NZ714538B2 - Antimicrobial compounds and compositions - Google Patents

Abstract

This invention is related to use of antimicrobial compounds and/or compositions against pathogens affecting meats, plants, or plant parts. In one embodiment, the provided antimicrobial compounds are volatile as adducted products of certain oxaborole moieties. Delivery systems are provided to take advantage of the volatile nature of these antimicrobial compounds and/or compositions. Also combinations with a volatile plant growth regulator, for example 1-methylcyclopropene, are disclosed. vantage of the volatile nature of these antimicrobial compounds and/or compositions. Also combinations with a volatile plant growth regulator, for example 1-methylcyclopropene, are disclosed.

Description

ANTIMICROBIAL COMPOUNDS AND COMPOSITIONS BACKGROUND OF THE INVENTION A number of compounds containing an oxaborole ring have been disclosed previously. r, there has been no teaching that these oxaborole compounds are volatile antimicrobial . In addition, these has been no teaching for ing or ating these oxaborole compounds while maintaining their antimicrobial activity and/or volatility.

Thus, there remains a need to develop new use of various volatile antimicrobial agents, and/or combination with a volatile plant growth regulator, in particular for agricultural applications.

SUMMARY OF THE INVENTION This ion is related to use of antimicrobial compounds and/or compositions against pathogens affecting meats, plants, or plant parts. In one embodiment, the provided antimicrobial compounds are le as adducted products of certain oxaborole moieties.

Delivery systems are provided to take advantage of the volatile nature of these antimicrobial compounds and/or compositions. Also combinations with a volatile plant growth regulator, for example l-methylcyclopropene, are disclosed.

In one aspect, provided is an antimicrobial compound having a structure of formula (A): RA — LA — G — LB — RB (A), n each of RA and RB is independently a l comprising an oxaborole moiety; R R R _;_ each of LA and LB is independently —O—, —N—, —B— —P—, or R' ; each ofR and R’ is independently hydrogen, unsubstituted or substituted C148 -alkyl, arylalkyl, aryl, or heterocyclic ; G is a tuted or unsubstituted C148 -alkylene, arylalkylene, arylene, or heterocyclic moiety; and agriculturally acceptable salts thereof In one embodiment, the antimicrobial nd is a le compound. In another embodiment, the antimicrobial compound has use against pathogens affecting meats, plants, or plant parts, comprising contacting the meats, plants, or plant parts. In another embodiment, the — LA — G — LB — portion of formula (A) is derived from a diol or diamine nd. In a fidrther embodiment, the diol compound is selected from the group consisting of 1,2-ethylene glycol; l,2-propylene ; l,3-propylene glycol; l,l,2,2-tetramethyl-l,2-ethylene glycol; 2,2- dimethyl-l,3-propylene glycol; l,6-hexanediol; l,lO-decanediol; and combinations thereof. In r ment, the diamine compound is l,2-ethylene diamine; l,3-propylene diamine; or combinations thereof. In another embodiment, each of LA and LB is independently —O— or —NH— . In another embodiment, LA and LB are identical. In another embodiment, LA and LB are different. In another embodiment, G is a substituted or unsubstituted C1_g —alkylene. In a fidrther embodiment, G is a substituted or unsubstituted C1_4 —alkylene. In a fidrther embodiment, G is selected from CH2 , CH2 CH2 ,and CH2 CH2 CH2 .

In another embodiment, each of RA and RB is independently derived from the group consisting of 5-fluoro- l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; 5 -chloro-l ,3 -dihydro- l - hydroxy-2, l -benzoxaborole; l ,3 -dihydro- l xy-2, l -benzoxaborole; and combinations thereof. In another embodiment, RA and RB are identical. In another embodiment, RA and RB are different.

In another embodiment, each of RA and RB is independently selected from formula (13), (C), (D), (E), (F), or (G): wherein ql and q2 are independently l, 2, or 3; q3 = 0, l, 2, 3, or 4; B is boron; M is hydrogen, halogen, -OCH3, or —CH2-O-CH2-O-CH3; M1 is halogen, , or —OCH3; X is o, s, or NR1“, wherein R10 is hydrogen, substituted alkyl, or unsubstituted alkyl; R1, Rla, Rlb, R2, and R5 are independently hydrogen, OH, NHZ, SH, CN, N02, SOZ, , OSOZNHZ, tuted or unsubstituted cycloalkyl, tuted or tituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R6(n)— l /O \ X2 (E) wherein each R6 is independently hydrogen, alkyl, alkene, alkyne, haloalkyl, haloalkene, kyne, alkoxy, alkeneoxy, haloalkoxy, aryl, aryl, arylalkyl, arylalkene, arylalkyne, heteroarylalkyl, heteroarylalkene, heteroarylalkyne, halogen, hydroxyl, nitrile, amine, ester, carboxylic acid, ketone, alcohol, sufide, sulfoxide, sulfone, sulfoximine, sulfilimine, sulfonamide, e, sulfonate, nitroalkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydrazone, carbamate, thiocarbamate, urea, thiourea, carbonate, aryloxy, or aryloxy; n =1, 2, 3, or 4; B is boron; X2 = (CR62)m where m = l, 2, 3, or 4; or D B/\ | {o A (F) wherein A and D together with the carbon atoms to which they are attached form a 5, 6, or 7-membered fused ring which may be substituted by C1_6 -alkyl, C1_6 -alkoxy, y, halogen, nitro, nitrile, amino, amino substituted by one or more C1_6 -alkyl groups, y, acyl, aryloxy, carbonamido, carbonamido substituted by C1_6 -alkyl, sulphonamido or trifluoromethyl or the fiJsed ring may link two oxaborole rings; B is boron; X1 is a group —CR7R8 wherein R7 and R8 are each independently hydrogen, C1_6 - alkyl, nitrile, nitro, aryl, l or R7 and R8 together with the carbon atom to which they are attached form an alicyclic ring; or R9 / R1031 B» \X3 0 (G) wherein R9 is CN, C(O)NR11R12, or C(O)OR13 wherein R13 is hydrogen, substituted alkyl, or unsubstituted alkyl, X3 is N, CH and CR“); R10 is halogen, substituted or unsubstituted alkyl, C(O)R14, C(O)OR14, OR”, NRMR15 wherein each of R11, R12, R14, and R15 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or tituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, tuted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and agriculturally acceptable salts thereof.

In another embodiment, the antimicrobial nd has a structure of formula (Al) or (A2): D1 \ D1 B B / \ / \ A] O 0 Al R16 R17 R16 R17 (Al) R13 R13 D2 N\/ D2 B B / \ / \ A2 0 0 A2 R18 R19 R18 R19 (A2) wherein each of A1, A2, D1, and D2 is independently hydrogen, substituted or tituted C148 -alkyl, arylalkyl, aryl, or heterocyclic; or A1 and D1, or A2 and D2 together form a 5, 6, or 7-membered fused ring which is substituted or unsubstituted; each of R16, R17, R18, and R19 is independently hydrogen, substituted or unsubstituted C1_6 -alkyl, nitrile, nitro, aryl or aryl alkyl; or R16 and R”, or R18 and R19 together form an alicyclic ring which is substituted or unsubstituted; B is boron; and G is a substituted or tituted €1-18 -alkylene, arylalkylene, arylene, or heterocyclic moiety; and lturally acceptable salts thereof.

In another embodiment, each of RA and RB is independently B/ B/ £10 CC/ /O F X2 wherein X2 = (CR62)In and m = l, 2, 3, or 4.

In another embodiment, each of RA and RB is independently ./ / In another embodiment, the antimicrobial compound has the structure of /O_\_ /©:>B O o /B F O\j©\ In another , provided is a mixture or composition sing the antimicrobial compound described herein. In one embodiment, the mixture of composition r comprises a cyclopropene compound. In a further embodiment, the cyclopropene compound is of the formula: - “'- - \\\\\\\\\ 1% :° wherein R is a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, WO 97634 phenyl, or naphthyl group; wherein the substituents are independently halogen, alkoxy, or substituted or unsubstituted phenoxy. In one embodiment, R is C1_g alkyl. In another embodiment, R is methyl.

In r embodiment, the cyclopropene compound is of the formula: R3 R4 R1 R2 wherein R1 is a substituted or tituted C1-C4 alkyl, C1-C4 alkenyl, C1-C4 alkynyl, C1-C4 cylcoalkyl, cylcoalkylalkyl, phenyl, or napthyl group; and R2, R3, and R4 are hydrogen. In another embodiment, the cyclopropene comprises l-methylcyclopropene ).

In r aspect, provided is a method of using an antimicrobial compound against pathogens affecting meats, , or plant parts. The method comprises contacting the meats, plants, or plant parts with an effective amount of the antimicrobial compound having a structure of formula (A): RA — LA — G — LB — RB (A), wherein each of RA and RB is independently a radical comprising an ole moiety; R R R _;_ each of LA and LB is independently —O—, —N—, —B— —P—, or R' ; each ofR and R’ is independently hydrogen, tituted or substituted C148 -alkyl, arylalkyl, aryl, or heterocyclic moiety; G is a substituted or unsubstituted C148 -alkylene, arylalkylene, arylene, or heterocyclic moiety; and agriculturally acceptable salts thereof In one embodiment, the antimicrobial compound is a volatile compound. In another embodiment, the — LA — G — LB — portion of formula (A) is derived from a diol or diamine compound. In a further embodiment, the diol compound is ed from the group consisting of l,2-ethylene glycol; l,2-propylene glycol; l,3-propylene glycol; l,l,2,2-tetramethyl-l,2-ethylene glycol; 2,2—dimethyl-l,3-propylene glycol; l,6-hexanediol; l,lO-decanediol; and ations thereof. In another embodiment, the e compound is l,2-ethylene diamine; l,3-propylene diamine; or combinations thereof In another ment, LA and LB are identical. In another embodiment, LA and LB are different. In another ment, each of LA and LB is independently —O— or —NH—. In another embodiment, LA and LB are identical. In another embodiment, LA and LB are different. In r embodiment, G is a substituted or unsubstituted C1_g —alkylene. In a further embodiment, G is a substituted or unsubstituted C1_4 —alkylene. In a further embodiment, Gis selected from CH2 , CH2 CH2 ,and CH2 CH2 CH2 .

In another embodiment, each of RA and RB is ndently derived from the group consisting of 5-fluoro- l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; 5 -chloro-l ,3 -dihydro- l - hydroxy-2, l -benzoxaborole; l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; and combinations f. In another embodiment, RA and Bb are identical. In another embodiment, RA and RB are different.

In r embodiment, each of RA and RB is independently selected from formula (13), (C), (D), (E), (F), or (G): wherein ql and q2 are independently l, 2, or 3; q3 = 0, l, 2, 3, or 4; B is boron; M is hydrogen, halogen, -OCH3, or —CH2-O-CH2-O-CH3; M1 is halogen, -CH2OH, or —OCH3; X is o, s, or NR1“, wherein R10 is en, substituted alkyl, or unsubstituted alkyl; R1, Rla, Rlb, R2, and R5 are ndently hydrogen, OH, NH2, SH, CN, N02, SO2, OSO2OH, OSO2NH2, tuted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or / B R (n)6 _ ] /o wherein each R6 is independently hydrogen, alkyl, alkene, alkyne, haloalkyl, haloalkene, haloalkyne, alkoxy, alkeneoxy, haloalkoxy, aryl, heteroaryl, arylalkyl, arylalkene, kyne, arylalkyl, arylalkene, heteroarylalkyne, n, hydroxyl, nitrile, amine, ester, carboxylic acid, ketone, alcohol, sufide, sulfoxide, sulfone, sulfoximine, sulfilimine, sulfonamide, e, sulfonate, nitroalkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydrazone, carbamate, thiocarbamate, urea, thiourea, carbonate, aryloxy, or heteroaryloxy; n = l, 2, 3, or 4; B is boron; X2 = (CR62)In where m = l, 2, 3, or 4; or D B/\ l {o A (F) wherein A and D together with the carbon atoms to which they are attached form a 5, 6, or 7-membered fused ring which may be substituted by C1_6 , C1_6 -alkoxy, hydroxy, halogen, nitro, nitrile, amino, amino substituted by one or more C1_6 -alkyl groups, carboxy, acyl, aryloxy, carbonamido, carbonamido substituted by C1_6 -alkyl, sulphonamido or trifluoromethyl or the fiJsed ring may link two oxaborole rings; B is boron; X1 is a group —CR7R8 wherein R7 and R8 are each ndently hydrogen, C1_6 - alkyl, nitrile, nitro, aryl, aralkyl or R7 and R8 together with the carbon atom to which they are attached form an alicyclic ring; or R9 / 3/ B 0 (G) wherein R9 is CN, C(O)NR11R12, or C(O)OR13 wherein R13 is hydrogen, substituted alkyl, or unsubstituted alkyl, X3 is N, CH and CR“); R10 is halogen, substituted or unsubstituted alkyl, 4, C(O)OR14, OR”, NRMR15 wherein each of R11, R12, R14, and R15 is independently hydrogen, tuted or tituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or tituted heteroaryl; and agriculturally acceptable salts thereof.

In another embodiment, the antimicrobial compound has a structure of formula (Al) or (A2): D1 /O/G\o\ D1 B B / \ / \ A] O 0 Al R16 R17 R16 R17 (Al) R13 R13 D2 \/N/G\N\/ D2 B B / \ / \ A2 0 0 A2 R18 R19 R18 R19 (A2) wherein each of A1, A2, D1, and D2 is independently hydrogen, substituted or unsubstituted C148 -alkyl, arylalkyl, aryl, or cyclic; or A1 and D1, or A2 and D2 together form a 5, 6, or 7-membered fused ring which is substituted or unsubstituted; each of R16, R17, R18, and R19 is independently hydrogen, substituted or unsubstituted C1_6 , nitrile, nitro, aryl or aryl alkyl; or R16 and R”, or R18 and R19 together form an alicyclic ring which is substituted or unsubstituted; B is boron; and G is a substituted or unsubstituted €1-18 -alkylene, arylalkylene, arylene, or heterocyclic ; and agriculturally acceptable salts thereof.

In another embodiment, each of RA and RB is independently B/ B/ \O \ / /O F X2 wherein X2 = (CR62)In and m = l, 2, 3, or 4.

In another embodiment, each of RA and RB is independently B/ / In another embodiment, the antimicrobial compound has the structure of DixOO B In one embodiment of the method provided, the en is selected from the group consisting ofAlternaria spp., Aspergillus spp., Botryospheria spp., Botrytis spp., Byssochlamys spp., Colletotrichum spp., Diploclia spp., Fusarium spp., Geotrichum spp., Lasiocliploclia spp., Monolinia spp., Mucor spp., Penicillium spp., Pezicula spp., Phomopsis spp., Phytophthora spp., Pythium spp., Rhizoctonia spp., Rhizopus spp., Sclerotinia spp., and Venturia spp. In another embodiment, the en is ed from the group consisting nia spp., Pectobacterium spp., Pseudomonas spp., Ralstonia spp., Xanthomonas spp.; Salmonella spp., Escherichia spp., Listeria spp., Bacillus spp., Shigella spp., and Staphylococcus spp. In r embodiment, the pathogen is selected from the group consisting of Candida spp., Debaryomyces spp., Bacillus spp., obacter spp., Clostriclium spp., Cryptosporidium spp., a spp., Vibrio spp., and Yersinia spp. In another embodiment, the method comprises a pre-harvest treatment or post- t treatment. In a fiarther embodiment, the pre-harvest treatment is selected from the group consisting of seed treatment and transplant treatment. In another embodiment, the post-harvest treatment is selected from the group ting of treatment during field packing, treatment during palletization, in-box treatment, treatment during transportation, and treatment during WO 97634 storage and/or throughout distribution network.

In another embodiment, the plants or plant parts comprise transgenic plants or transgenic plant parts. In another embodiment, the plants or plant parts are selected from the group consisting of corn, wheat, , rice, soybean, and canola. In another ment, the plants or plant parts are selected from the group ting of fruit, vegetables, nursery, turf and ornamental crops. In a further embodiment, the fruit is selected from the group consisting of banana, pineapple, citrus including oranges, lemon, lime, grapefruit, and other citrus, grapes, watermelon, cantaloupe, muskmelon, and other melons, apple, peach, pear, cherry, kiwifruit, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig, and berries including strawberry, blueberry, raspberry, blackberry, currents and other types of berries. In a fiarther embodiment, the vegetable is selected from the group consisting of tomato, potato, sweet , cassava, pepper, bell pepper, carrot, celery, squash, eggplant, cabbage, cauliflower, broccoli, gus, mushroom, onion, garlic, leek, and snap bean. A filrther ment, the flower or flower part is selected from the group consisting of roses, camations, orchids, geraniums, lily or other ornamental flowers. A further ment, the meat is ed from the group of beef, bison, chicken, deer, goat, turkey, pork, sheep, fish, shellfish, mollusks, or red meat products.

In one embodiment, the ting comprises applying the volatile antimicrobial compound by ways selected from the group consisting of spray, mist, thermal or non-thermal fogging, drench, gas treatment, and combinations thereof. In a further embodiment, the gas treatment is selected from the group consisting of release from a sachet, release from a synthetic or natural film, fibrous material, and/or release from liner or other packaging materials, e from powder, release from a leasing generator, e using a compressed or non- compressed gas cylinder, release from a droplet inside a box, and combinations thereof. In r embodiment, the method further comprises contacting the meats, plants, plant parts with a volatile plant growth regulator. In a further ment, the volatile plant growth regulator is a cyclopropene compound. In a further embodiment, the cyclopropene compound comprises 1- methylcyclopropene (l -MCP).

In another aspect, provided is a method of preparing an antimicrobial compound. The method comprises: (a) mixing at least one oxaborole compound with at least one adducting compound in a first 2014/040960 organic solvent; (b) evaporating the first organic solvent by heating, thereby allowing the at least one adducting compound to react with the at least one oxaborole compound to generate at least one adducted product; and (c) crystallizing the at least one adducted product using a second organic solvent.

In one embodiment, the first organic solvent is same as the second organic t.

In another embodiment, the first c solvent is toluene. In another embodiment, the first organic solvent is different than the second organic solvent. In another ment, the second solvent is toluene or hexane. In another embodiment, the second solvent is hexane.

In r embodiment, the heating is performed at a ature between 110 0C and 1250 0C; between 100 0C and 150 0C; or between 18 0C and 200 0C In r embodiment, the at least one adducting compound comprises a diol or diamine compound. In a further embodiment, the diol compound is selected from the group consisting of l,2-ethylene glycol; l,2-propylene ; l,3-propylene glycol; l,l,2,2- tetramethyl-l,2-ethylene glycol; 2,2-dimethyl-l,3-propylene glycol; l,6-hexanediol; l,lO- decanediol; and combinations thereof In another embodiment, the diamine compound is l,2- ethylene e; l,3-propylene diamine; or combinations thereof.

In another embodiment, the at least one oxaborole compound comprises a compound ofa structure selected from formula (B1), (C1), (D1), (E1), (F1), or (G1): (D1), R9\/ B/ EOE/l \O \X3 0 (G1) wherein R* is —OH and the other substituents are as defined herein for formula (B), (C), (D), (E), (F), or (G).

In another embodiment, the at least one oxaborole compound comprises a compound selected from the group consisting of 5-fluoro-l,3-dihydro-l-hydroxy-2,1-benzoxaborole; 5- chloro-l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; and combinations f.

In another embodiment, the at least one oxaborole nd comprises a compound of a structure ed from OH OH B/ / | I \ \ F X2 wherein X2 = (CR62)In and m = l, 2, 3, or 4.

In another embodiment, the at least one oxaborole compound comprises a compound of a structure selected from /OH OH B / 090 OLD\ B\ F or .

In another embodiment, the at least one adducted product comprises a nd having a structure of formula (Al) or (A2): D1 o/G\o D1 B/ \B / \ / \ A] O 0 Al R16 R17 R16 R17 (Al) WO 97634 R13 /R13 D2 N/G\N D2 B/ \B / \ / \ A2 O O A2 R18 R19 R18 R19 (A2) wherein the substituents are as defined herein for formula (Al) or (A2).

In another embodiment, wherein the at least one adducted product comprises a compound having a structure of O_\_ o /B In another embodiment, step (a) is performed at a temperature between 50 0C and 60 0C; between 40 0C and 80 0C or between 20 0C and 120 0C.

In r embodiment, step (a) is performed in ce of at least one catalyst. In a further embodiment, the catalyst is selected from the group consisting of amine, phosphine, heterocyclic nitrogen, um, phosphonium, arsonium, sulfonium moieties, and combinations thereof. In another embodiment, the catalyst is selected from the group consisting of a onium compound, an ammonium compound, chromium salts, amino compounds and combinations thereof. In another embodiment, the catalyst is selected from the group consisting of yl imidazole, 2-phenyl imidazole, an imidazole derivative, l,8-diazabicyclo[5.4.0] undecene (DBU), and combinations thereof DETAILED PTION OF THE INVENTION This invention is based on surprising results that two to one adduct of oxaborole compounds can (1) possess volatile property at room temperature; and (2) have antimicrobial activity against for example fungi, especially Botrytis cinerea. One e includes the two to one adduct of 5-fluoro-l-hydroxy-2,l-benzoxaborole which shows excellent activity against Botrytis cinerea. Volatile antimicrobial agents (for example ides) have utility in postharvest disease control. Provided are methods using reaction of certain l- hydroxybenzoxaborole compounds with certain diol compounds to form compounds having antimicrobial activity, and compounds and/or composition prepared by the methods disclosed.

Unless otherwise stated, the following terms used in this application, including the specification and claims, have the definitions given below. It must be noted that, as used in the specification and the appended claims, the singular forms CC 3, (C a an,” and “the” e plural nts unless the context clearly dictates otherwise. Definition of rd chemistry terms may be found in nce works, including Carey and Sundberg, Advanced Organic Chemistry 4th Ed., Vols. A (2000) and B (2001), Plenum Press, New York, NY.

As used herein, the phrase “moiety” refers to a specific segment or functional group of a molecule. al moieties are often recognized chemical entities embedded in or appended to a molecule.

As used herein, the phrases “heteroatom” and “hetero-“ refer to atoms other than carbon (C) and hydrogen (H). Examples of heteroatoms include oxygen (0), en (N) sulfur (S), silicon (Si), germanium (Ge), aluminum (Al) and boron (B).

As used herein, the phrases “halo” and en” are hangeable and refer to fiuoro (-F), chloro (-Cl), bromo (-Br), and iodo (-I).

As used herein, the phrase “alkyl” refers to an unsubstituted or substituted, hydrocarbon group and can include straight, branched, cyclic, saturated and/or unsaturated features. Although the alkyl moiety may be an “unsaturated alkyl” moiety, which means that it contains at least one alkene or alkyne moiety, typically, the alkyl moiety is a “saturated alkyl” group, which means that it does not contain any alkene or alkyne moieties. Likewise, although the alkyl moiety may be a cyclic, typically the alkyl moiety is a non-cyclic group. Thus, in some embodiments, “alkyl” refers to an optionally substituted straight-chain, or optionally substituted branched-chain saturated hydrocarbon monoradical having from about one to about thirty carbon atoms in some embodiments, from about one to about fifteen carbon atoms in some ments, and from about one to about six carbon atoms in filrther ments. Examples of saturated alkyl ls include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2- methyl-l-propyl, ylpropyl, 2-methyl- l -butyl, yl- l -butyl, 2-methyl-3 -butyl, 2,2- dimethyl- l l, 2-methyl- l -pentyl, 3 -methylpentyl, 4-methyl- l -pentyl, 2-methylpentyl, 3-methylpentyl, ylpentyl, 2,2-dimethyl-l-butyl, 3,3-dimethyl-l-butyl, 2-ethyl- l - butyl, butyl, isobutyl, tyl, t-butyl, n-pentyl, isopentyl, neopentyl, and n-hexyl, and longer alkyl groups, such as heptyl, and octyl. It should be noted that whenever it appears herein, a cal range such as “l to 6” refers to each integer in the given range; e.g., “l to 6 carbon atoms” or “C1_6” or “C1-C6” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, and/or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is ated.

As used herein, the phrase “substituted alkyl” refers to an alkyl group, as defined herein, in which one or more (up to about five, preferably up to about three) hydrogen atoms is replaced by a substituent independently selected from the substituent group defined herein.

As used herein, the phrases “substituents” and “substituted” refer to groups which may be used to replace another group on a molecule. Such groups are known to those of skill in the al arts and may include, without tion, one or more of the following independently selected , or ated subsets thereof: halogen, -CN, -OH, -N02, -N3, =0, =S, =NH, -SOz, -NH2, -COOH, -S(Oz), nitroalkyl, amino, including mono- and di-substituted amino groups, cyanato, isocyanato, thiocyanato, isothiocyanato, guanidinyl, O-carbamyl, N- carbamyl, rbamyl, uryl, isouryl, thiouryl, isothiouryl, mercapto, sulfanyl, sulfinyl, sulfonyl, sulfonamidyl, phosphonyl, phosphatidyl, oramidyl, dialkylamino, diarylamino, diarylalkylamino; and the ted compounds thereof The protecting groups that may form the protected compounds of the above substituents are known to those of skill in the art and may be found in nces such as Greene and Wuts, Protective Groups in Organic sis, 3d Ed., John Wiley & Sons, New York, NY. (1999) and Kocienski, Protective Groups, Thieme Verlag, New York, NY. (1994) which are incorporated herein by reference in their entirety.

As used herein, the phrase “alkoxy” refers to the group —O-alkyl, where alkyl is as defined herein. In one ment, alkoxy groups include, e.g., methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like. The alkoxy can be unsubstituted or substituted.

As used herein, the phrases “cyclic” and “membered ring” refer to any cyclic structure, including alicyclic, heterocyclic, aromatic, heteroaromatic and polycyclic filsed or non- fused ring systems as described herein. The term “membered” is meant to denote the number of skeletal atoms that constitute the ring. Thus, for example, pyridine, pyran, and pyrimidine are six-membered rings and e, tetrahydrofuran, and thiophene are f1ve-membered rings.

As used herein, the phrase “aromatic” refers to a cyclic or polycyclic moiety having a conjugated unsaturated (411+2)TE electron system (where n is a positive integer), sometimes referred to as a delocalized 715 electron system.

As used herein, the phrase “aryl” refers to an ally substituted, aromatic, cyclic, hydrocarbon monoradical of from six to about twenty ring atoms, preferably from six to about ten carbon atoms and includes fused (or condensed) and non-fused aromatic rings. A fused aromatic ring radical contains from two to four fiJsed rings where the ring of attachment is an aromatic ring, and the other dual rings within the fused ring may be cycloalkyl, cycloalkenyl, lkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aromatic, heteroaromatic or any combination thereof A non-limiting example of a single ring aryl group es phenyl; a fused ring aryl group includes naphthyl, anthryl, azulenyl; and a non-fused bi- aryl group includes biphenyl.

As used herein, the phrase “substituted aryl” refers to an aryl group, as defined , in which one or more (up to about five, preferably up to about three) hydrogen atoms is replaced by a substituent independently selected from the group defined herein, (except as otherwise constrained by the definition for the aryl tuent).

As used herein, the phrase “heteroaryl” refers to an optionally substituted, aromatic, cyclic monoradical containing from about five to about twenty skeletal ring atoms, preferably from five to about ten ring atoms and includes fused (or condensed) and non-fused aromatic rings, and which have one or more (one to ten, preferably about one to about four) ring atoms selected from an atom other than carbon (2'.e., a heteroatom) such as, for example, oxygen, nitrogen, sulfur, selenium, phosphorus or combinations thereof. The term aryl includes ally substituted fused and sed heteroaryl ls having at least one heteroatom. A fused heteroaryl radical may contain from two to four fused rings where the ring of attachment is a heteroaromatic ring and the other individual rings within the fused ring system may be alicyclic, heterocyclic, aromatic, heteroaromatic or any combination thereof The term heteroaryl also includes fused and non-fused heteroaryls having from five to about twelve skeletal ring atoms, as well as those having from five to about ten skeletal ring atoms. Examples of heteroaryl groups include, but are not limited to, acridinyl, benzo[l,3]dioxole, benzimidazolyl, benzindazolyl, sooxazolyl, benzokisazolyl, lranyl, benzofurazanyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, b]thienyl, benzothiophenyl, benzothiopyranyl, benzotriazolyl, benzoxazolyl, carbazolyl, carbolinyl, chromenyl, cinnolinyl, filranyl, furazanyl, furopyridinyl, filryl, olyl, indazolyl, indolyl, indolidinyl, indolizinyl, isobenzofuranyl, isoindolyl, isoxazolyl, isoquinolinyl, isothiazolyl, naphthylidinyl, naphthyridinyl, oxadiazolyl, oxazolyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxathiynyl, thianthrenyl, phenathridinyl, phenathrolinyl, phthalazinyl, pteridinyl, purinyl, puteridinyl, pyrazyl, pyrazolyl, pyridyl, nyl, pyridazinyl, pyrazinyl, pyrimidinyl, dyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, olyl, azolyl, thiazolyl, thienyl, triazinyl, (l,2,3,)— and (1,2,4)- triazolyl and the like, and their oxides where appropriate, such as for example pyridyl-N—oxide.

As used , the phrase “substituted heteroaryl” refers to a heteroaryl group, as defined herein, in which one or more (up to about five, preferably up to about three) hydrogen atoms is replaced by a tuent independently selected from the group defined herein.

As used herein, the phrase “leaving group” refers to a group with the meaning conventionally associated with it in tic organic chemistry, i.e., an atom or group displaceable under substitution reaction conditions. Examples of leaving groups include, but are not limited to, halogen, alkane- or esulfonyloxy, such as methanesulfonyloxy, ethanesulfonyloxy, thiomethyl, benzenesulfonyloxy, tosyloxy, and thienyloxy, dihalophosphinoyloxy, optionally substituted benzyloxy, isopropyloxy, acyloxy, and the like. In some embodiments, a leaving group can be HC(O)—COOH or RC(O)—COOH, wherein R is a C1- C6 alkyl or substituted C1-C6 alkyl.

] The compounds of the invention as described herein may be synthesized using standard synthetic techniques known to those of skill in the art or using methods known in the art in combination with s described herein. The starting materials used for the synthesis of the compounds of the invention as described herein, can be obtained from commercial sources, such as Aldrich al Co. (Milwaukee, Wis.), Sigma Chemical Co. (St. Louis, M0), or the starting materials can be synthesized. The nds described herein, and other related compounds having different substituents can be synthesized using techniques and materials known to those of skill in the art, such as described, for example, in March, Advanced Organic Chemistry 4th Ed. (1992) John Wiley & Sons, New York, N.Y.; Carey and Sundberg, Advanced Organic try 4th Ed., Vols. A (2000) and B (2001) Plenum Press, New York, NY. and Greene and Wuts, tive Groups in Organic Synthesis, 3rd Ed. (1999) John Wiley & Sons, New York, N.Y., (all of which are incorporated by reference in their entirety). General methods for the preparation of compound as disclosed herein may be derived from known reactions in the field, and the reactions may be modified by the use of appropriate reagents and conditions, as would be recognized by the skilled , for the introduction of the various moieties found in the ae as provided herein. For e, the compounds described herein can be modified using various electrophiles or nucleophiles to form new functional groups or substituents.

In one aspect, provided is an antimicrobial compound having a structure of formula (A): RA — LA — G — LB — RB (A), wherein each of RA and RB is independently a radical comprising an oxaborole moiety; R R R _;_ each of LA and LB is independently —O—, —N—, —B— —P—, or R' ; each ofR and R’ is independently hydrogen, unsubstituted or substituted C148 -alkyl, arylalkyl, aryl, or heterocyclic moiety; and G is a substituted or unsubstituted C148 -alkylene, arylalkylene, arylene, or cyclic moiety.

In one ment, the antimicrobial compound is a volatile compound. In another embodiment, the — LA — G — LB — portion of formula (A) is derived from a diol or diamine compound. In a further embodiment, the diol compound is selected from the group consisting of hylene glycol; l,2-propylene glycol; l,3-propylene glycol; l,l,2,2-tetramethyl-l,2-ethylene glycol; 2,2—dimethyl-l,3-propylene glycol; l,6-hexanediol; ecanediol; and combinations thereof. In another embodiment, the diamine compound is l,2-ethylene diamine; opylene e; or combinations thereof In another embodiment, LA and LB are identical. In another embodiment, LA and LB are different. In another embodiment, each of LA and LB is independently —O— or —NH—. In another embodiment, LA and LB are identical. In another embodiment, LA and LB are different. In another embodiment, G is a substituted or unsubstituted C1_g —alkylene. In a further embodiment, G is a substituted or unsubstituted C1_4 —alkylene. In a r embodiment, Gis selected from CH2 , CH2 CH2 ,and CH2 CH2 CH2 .

In another embodiment, each of RA and RB is independently d from the group consisting of 5-fluoro- l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; 5 o-l ,3 -dihydro- l - hydroxy-2, l -benzoxaborole; l ,3 -dihydro- l -hydroxy-2, l -benzoxaborole; and combinations f. In r embodiment, RA and RB are identical. In another embodiment, RA and RB are different.

In another embodiment, at least one of RA and RB is selected from formula (B), (C), or (D): wherein ql and q2 are independently l, 2, or 3; q3 = 0, l, 2, 3, or 4; [001 10] B is boron; M is hydrogen, halogen, -OCH3, or —CH2-O-CH2-O-CH3; M1 is halogen, -CH20H, or —OCH3; X is o, s, or NR1“, wherein R10 is hydrogen, substituted alkyl, or unsubstituted alkyl; R1, Rla, Rlb, R2, and R5 are independently hydrogen, OH, NHZ, SH, CN, N02, 802, OSOZOH, OSOZNHZ, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, tuted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and agriculturally acceptable salts thereof Additional oxaborole moieties are also disclosed previously in US. Patent No. 8,106,031, and International Patent Application WC 3 lO72A2, the contents of which are hereby orated by reference in their entireties.

In another embodiment, at least one of RA and RB has a ure of a (F): wherein A and D together with the carbon atoms to which they are attached form a 5, 6, or 7-membered fused ring which may be substituted by C1_6 -alkyl, C1_6 -alkoxy, y, halogen, nitro, nitrile, amino, amino substituted by one or more C1_6 -alkyl groups, y, acyl, aryloxy, carbonamido, amido substituted by C1_6 -alkyl, sulphonamido or trifluoromethyl or the fidsed ring may link two oxaborole rings; B is boron; ] X1 is a group —CR7R8 wherein R7 and R8 are each independently hydrogen, C1_6 - alkyl, nitrile, nitro, aryl, aralkyl or R7 and R8 together with the carbon atom to which they are attached form an alicyclic ring; and ] and agriculturally acceptable salts thereof.

Additional oxaborole moieties are also disclosed usly in US. Patent No. ,880,188, the content of which is hereby incorporated by reference in its entirety.

In another embodiment, at least one of RA and RB is selected from a (E) or (G): / B R (n)6 _ l /O \ X2 (E) n each R6 is independently hydrogen, alkyl, alkene, , haloalkyl, haloalkene, haloalkyne, alkoxy, oxy, haloalkoxy, aryl, heteroaryl, arylalkyl, arylalkene, arylalkyne, heteroarylalkyl, heteroarylalkene, heteroarylalkyne, halogen, hydroxyl, e, amine, ester, carboxylic acid, ketone, alcohol, suf1de, sulfoxide, sulfone, sulfoximine, sulfilimine, sulfonamide, sulfate, sulfonate, nitroalkyl, amide, oxime, imine, hydroxylamine, hydrazine, hydrazone, carbamate, thiocarbamate, urea, thiourea, carbonate, aryloxy, or heteroaryloxy; n =1, 2, 3, or 4; B is boron; X2 = (CR62)In where m = 1, 2, 3, or 4; or R9 / / B \X3 0 (G) n R9 is CN, C(O)NR11R12, or C(O)OR13 wherein R13 is hydrogen, substituted alkyl, or unsubstituted alkyl, X3 is N, CH and CR“); R10 is halogen, substituted or unsubstituted alkyl, C(O)R14, C(O)OR14, OR”, NRMR15 wherein each of R11, R12, R14, and R15 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted lkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and agriculturally able salts thereof.

In a filrther embodiment when at least one of RA and RB has a structure of formula (G), R9 is NC and R10 is Rb.

In r embodiment, at least one of RA and RB has a structure selected from: f m if agar} r4"- \' +3“- 5 [I < v ‘- =5 ' a R S3 53 ‘ 1 'v -' :\‘ “mm“ '1 ‘n :, u y 3: :5" “g“ s; S 1 i \r . 5; I E: {E-\ :; itt I“ r z ,- . -, .\ -.u- In r embodiment, at least one of RA and RB has a structure selected from: l l. ”G '3.\EI 'i: (11111111 IIIIIIIIII ”III/III}:III/1111’; f- aw._,L .. I “a";43" I.I?”a “a K‘s .

In another embodiment, at least one of RA and RB has a structure selected from: ’ ”M am M. 4%"- " “fl [1“ ‘ ; E?“ offikvfd wE KN’JA‘“H" , J 9 9 a,‘.‘-‘.l" N a. 4"" “k ‘mxfif‘xfi‘kfix‘x gffiy “9—" H» u k “k i it: ss (a):f In another embodiment when at least one of RA and RB has a structure of formula (G), R9 is —COOR3 and R10 is Rb.

In another ment, at least one of RA and RB has a structure selected from: >, 5 Mai-"’9 ~ “"9“ v}...“1* if lv.") 5E ti? u M2 2 21 2: 2 ti ‘3 N in? LM‘ 3‘ 22 ~ - 2: ‘ H. n '{~- " L' a a I»! g guf-IR} a” ' - L \ x W ts" ., 2; 2 ~- ‘3 xxxii'n 3 S: ES -"3 :2 i is \2 ~ 21 ,2”- Wxfix(fiffi%fl%fM In r embodiment, at least one of RA and RB has a structure selected from: 1 ‘ KS: ’32., v </ N z t S§ i W 2film\x§$33 2,.2.2“]. 2 s x ss u \ 0 -, é“. 55’3“! ; .2: a,» «9" R . j ._ 125A I», \= «,2 21* “Vxfirk‘a ,2!“ ‘3xxfk'fi In another embodiment, at least one of RA and RB has a structure selected from: .s 31034;" 2* _.«*‘-"“'N-§K 3“ -, R5 .~ ,. "-"-}"M,\ xfi.

\ \“ (W l 8,, ”an” ,— In another embodiment when at least one of RA and RB has a structure of formula (G), R9 is —CONR1R2 and R10 is Rb.

In another embodiment, the volatile antimicrobial compound of the ion is selected from: 2014/040960 2:222:22 :23 In r embodiment, the volatile antimicrobial compound of the invention is selected from: (M21213: 2 In another embodiment, the volatile antimicrobial compound of the invention is selected from: Ext:f)\R;E: In one embodiment, Rb is selected from fluorine and chlorine. In another embodiment, Rb is selected from OR20 and NRZIRZZ. In r embodiment when Rb is ORZO, R20 is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted WO 97634 heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or tituted heteroaryl. 20 In another embodiment when Rb is OR ,R is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl. In another embodiment when Rb is OR20 20 ,R is unsubstituted C1_6 alkyl. In another embodiment when Rb is ORZO, R20 is unsubstituted cycloalkyl. In another embodiment when Rb is ORZO, R20 is alkyl, substituted with a member ed from substituted or unsubstituted C1_6 alkoxy. In another embodiment when Rb is OR20 20 ,R is alkyl, substituted with at least one halogen. In another embodiment when Rb ORZO, R20 is alkyl, substituted with at least one oxo moiety.

In another embodiment when Rb is ORZO, R20 is a member selected from -CH3, - CH2CH3, -(CH2)2CH3, -CH(CH3)2, -CH2CF3, -CH2CHF2, -CH2CH2(OH), -CH2CH2(OCH3), - CH2CH2(OC(CH3)2), -C(O)CH3, -CH2CHZOC(O)CH3, -CH2C(O)OCH2CH3, - )OC(CH3)3, -(CH2)3C(O)CH3, -CH2C(O)OC(CH3)3, cyclopentyl, cyclohexyl, . ..s: 5 m5? ' fax“ ‘35:? fix a ' E ,3 - \ 1" J ”‘33"! 9 °' L T M - g \in-“3 and \z‘ 9 , In r ment when Rb is NRZIRZZ, R21 and R22 are members independently selected from H, substituted or unsubstituted alkyl, tuted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. In another embodiment when Rb is NRZIRZZ, R21 is H or unsubstituted alkyl; and R22 is unsubstituted alkyl or alkyl tuted with a member selected from hydroxyl, phenyl, unsubstituted alkoxy and alkoxy tuted with a phenyl. In a further embodiment when Rb is NRZIRZZ, R21 is H or CH3.

In another embodiment when Rb is NRZIRZZ, R21 and R22 are independently selected from substituted or unsubstituted alkyl. In another embodiment when Rb is Z, R21 is unsubstituted alkyl; and R22 is substituted or unsubstituted alkyl. In another embodiment when Rb is NRZIRZZ, R21 is unsubstituted alkyl; and R22 is alkyl, substituted with a member selected from substituted or unsubstituted alkoxy and hydroxyl. In another embodiment when Rb is NRZIRZZ, R21 is unsubstituted alkyl; and R22 is alkyl, substituted with unsubstituted alkoxy. In another embodiment when Rb is NRZIRZZ, R21 is unsubstituted alkyl; and R22 is alkyl, substituted with alkoxy, substituted with phenyl. In r ment when Rb is NRZIRZZ, R21 is unsubstituted alkyl; and R22 is alkyl, substituted with unsubstituted alkoxy. In another embodiment when Rb is NRZIRZZ, R21 and R22 together with the nitrogen to which they are attached, are combined to form a 4- to 8-membered substituted or unsubstituted heterocycloalkyl ring. In another embodiment when Rb is NRZIRZZ, R21 and R22 er with the nitrogen to which they are ed, are combined to form a 5- or 6-membered substituted or unsubstituted heterocycloalkyl ring.

In another embodiment, Rb is selected from N(CH3)2, N(CH3)(CH2CH2(OCH3)), N(CH3)(CH2CH20H), NHZ, NHCHg, NH(CH2CH2(OCH3)), NH(CH2CH2(OCH2Ph), NH(CH2Ph), H3)3) and NH(CH2CH20H). In r embodiment, Rb is selected from a. “a ‘3 x “a ,«H JIXN\ ‘3 (”(31 vV-L‘r i! \ l N H l . h (I‘M >4 JAE_"L-“‘ ,“we; K. ‘w’ I} and O‘v‘ , , Additional oxaborole moieties are also sed previously in US. patent No. 8,039,450, and patent application publication US 2009/0291917, the contents of which are hereby incorporated by reference in their entireties.

In another embodiment, the antimicrobial compound has a structure of a (Al) or (A2): D1 O/G\O D1 B \B / \ / \ A] O 0 Al R16 R17 R16 Rl7 (Al) R13 R13 D2 / D2 B/ \B / \ / \ A2 O O A2 R18 R19 R18 R19 (A2) wherein each of A1, A2, D1, and D2 is independently hydrogen, substituted or unsubstituted C148 -alkyl, arylalkyl, aryl, or heterocyclic; or A1 and D1, or A2 and D2 together form a 5, 6, or 7-membered fused ring which is substituted or unsubstituted; each of R16, R17, R18, and R19 is ndently hydrogen, substituted or unsubstituted C1_6 -alkyl, nitrile, nitro, aryl or aryl alkyl; or R16 and R”, or R18 and R19 together form an lic ring which is substituted or unsubstituted; B is boron; and ] G is a substituted or unsubstituted €1-18 -alkylene, arylalkylene, arylene, or heterocyclic moiety.

In r embodiment, each of RA and RB is independently / B/ B\ \ F X2 wherein X2 = (CR62)m and m = l, 2, 3, or 4.

In another embodiment, each of RA and RB is independently B B/ i l \ ,0 (:1)o F or .

In another embodiment, the antimicrobial compound has the structure of /O—\_ DDB 0 o /B ] The practice of the present invention involves the use of one or more cyclopropene compound. As used herein, a cyclopropene compound is any compound with the formula R3 R4 2014/040960 Where each R1, R2, R3 and R4 is independently ed from the group consisting of H and a chemical group of the formula: _(L)n'z Where n is an integer from 0 to 12. Each L is a bivalent radical. Suitable L groups include, for example, radicals containing one or more atoms selected from H, B, C, N, O, P, S, Si, or mixtures f. The atoms within an L group may be connected to each other by single bonds, double bonds, triple bonds, or mixtures thereof. Each L group may be , branched, cyclic, or a combination thereof In any one R group (i.e., any one of R1, R2, R3 and R4) the total number of atoms (i.e., atoms that are neither H nor C) is from 0 to 6. Independently, in any one R group the total number of non-hydrogen atoms is 50 or less. Each Z is a monovalent radical. Each Z is independently ed from the group consisting of hydrogen, halo, cyano, nitro, nitroso, azido, chlorate, bromate, iodate, isocyanato, isocyanido, isothiocyanato, pentafluorothio, and a chemical group G, wherein G is a 3 to 14 membered ring system.

The R1, R2, R3, and R4 groups are independently selected from the suitable groups.

Among the groups that are le for use as one or more of R1, R2, R3, and R4 are, for example, aliphatic , aliphatic-oxy groups, alkylphosphonato groups, cycloaliphatic groups, cycloalkylsulfonyl , cycloalkylamino groups, heterocyclic groups, aryl groups, heteroaryl groups, halogens, silyl groups, other groups, and mixtures and combinations thereof. Groups that are suitable for use as one or more of R1, R2, R3, and R4 may be substituted or unsubstituted.

Among the suitable R1, R2, R3, and R4 groups are, for example, aliphatic groups.

Some suitable tic groups include, for example, alkyl, alkenyl, and alkynyl groups. Suitable tic groups may be linear, branched, cyclic, or a combination f Independently, suitable aliphatic groups may be substituted or unsubstituted.

As used herein, a chemical group of interest is said to be “substituted” if one or more hydrogen atoms of the chemical group of interest is replaced by a substituent.

Also among the suitable R1, R2, R3, and R4 groups are, for example, substituted and unsubstituted heterocyclyl groups that are connected to the cyclopropene compound through an intervening oxy group, amino group, carbonyl group, or sulfonyl group; examples of such R1, R2, R3, and R4 groups are heterocyclyloxy, heterocyclylcarbonyl, rocyclylamino, and diheterocyclylaminosulfonyl.

Also among the le R1, R2, R3, and R4 groups are, for example, substituted and unsubstituted heterocyclic groups that are connected to the cyclopropene compound through an intervening oxy group, amino group, carbonyl group, sulfonyl group, thioalkyl group, or aminosulfonyl group; examples of such R1, R2, R3, and R4 groups are diheteroarylamino, heteroarylthioalkyl, and diheteroarylaminosulfonyl.

Also among the suitable R1, R2, R3, and R4 groups are, for example, hydrogen, fluoro, , bromo, iodo, cyano, nitro, nitroso, azido, chlorato, bromato, iodato, isocyanato, isocyanido, isothiocyanato, pentafluorothio; acetoxy, thoxy, cyanato, nitrato, nitrito, perchlorato, allenyl, butylmercapto, diethylphosphonato, dimethylphenylsilyl, isoquinolyl, mercapto, naphthyl, phenoxy, phenyl, piperidino, pyridyl, quinolyl, triethylsilyl, trimethylsilyl; and substituted analogs thereof.

] As used herein, the chemical group G is a 3 to 14 membered ring system. Ring systems suitable as chemical group G may be substituted or tituted; they may be aromatic (including, for example, phenyl and napthyl) or aliphatic (including unsaturated aliphatic, partially saturated aliphatic, or saturated tic); and they may be carbocyclic or heterocyclic.

Among cyclic G groups, some suitable heteroatoms are, for example, nitrogen, sulfur, oxygen, and combinations thereof. Ring systems suitable as chemical group G may be monocyclic, bicyclic, lic, polycyclic, spiro, or fused; among suitable chemical group G ring systems that are bicyclic, tricyclic, or fused, the various rings in a single chemical group G may be all the same type or may be of two or more types (for example, an ic ring may be fused with an aliphatic ring).

] In one embodiment, one or more of R1, R2, R3, and R4 is hydrogen or(C1-C10) alkyl.

In another embodiment, each of R1, R2, R3, and R4 is en or (C1-C8) alkyl. In r embodiment, each of R1, R2, R3, and R4 is en or ) alkyl. In another embodiment, each of R1, R2, R3, and R4 is hydrogen or methyl. In another embodiment, R1 is (C1-C4) alkyl and each of R2, R3, and R4 is hydrogen. In another embodiment, R1 is methyl and each of R2, R3, and R4 is hydrogen, and the cyclopropene compound is known herein as l-methylcyclopropene or “l-MCP.” In another embodiment, the cyclopropene is of the formula: . \\\\\\\\\\\\\\V {7* 355..N . wherein R is a substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, phenyl, or naphthyl group; wherein the substituents are independently halogen, alkoxy, or substituted or unsubstituted phenoxy. In one embodiment, R is C1_g alkyl. In another embodiment, R is methyl.

In another embodiment, the cyclopropene is of the a: R3 R4 R1 R2 wherein R1 is a substituted or tituted C1-C4 alkyl, C1-C4 alkenyl, C1-C4 alkynyl, C1-C4 cylcoalkyl, cylcoalkylalkyl, phenyl, or napthyl group; and R2, R3, and R4 are hydrogen. In another ment, the cyclopropene comprises l-methylcyclopropene (l-MCP).

As used herein, the phrase “transgene vector” refers to a vector that contains an inserted segment of DNA, the “transgene” that is transcribed into mRNA or replicated as RNA within a host cell. The phrase “transgene” refers not only to that portion of inserted DNA that is converted into RNA, but also those portions of the vector that are necessary for the transcription or replication of the RNA. A transgene typically comprises a gene-of—interest but needs not necessarily comprise a polynucleotide ce that contains an open reading frame capable of producing a protein.

Meats, plants, or plant parts may be d in the practice of the t invention.

One example is treatment of whole plants; another example is treatment of whole plants while they are planted in soil, prior to the harvesting of useful plant parts.

Any plants that provide useful plant parts may be treated in the practice of the present invention. Examples e plants that provide fruits, vegetables, and grains.

As used , the phrase “plant” includes dicotyledons plants and monocotyledons plants. es of dicotyledons plants include o, opsis, soybean, tomato, papaya, canola, sunflower, cotton, alfalfa, potato, grapevine, pigeon pea, pea, Brassica, chickpea, sugar beet, rapeseed, watermelon, melon, , peanut, pumpkin, radish, spinach, squash, broccoli, cabbage, carrot, cauliflower, celery, Chinese cabbage, cucumber, eggplant, and lettuce.

Examples of monocotyledons plants include com, rice, wheat, sugarcane, barley, rye, sorghum, orchids, bamboo, banana, cattails, lilies, oat, onion, millet, and triticale. Examples of fruit include banana, pineapple, oranges, grapes, ruit, watermelon, melon, , peaches, pears, kiwifruit, mango, nectarines, guava, persimmon, avocado, lemon, fig, and berries.

Those skilled in the art would understand certain variation can exist based on the disclosure provided. Thus, the following examples are given for the purpose of illustrating the invention and shall not be construed as being a tion on the scope of the invention or claims.

Example 1 — Preparation of Sample 1 3.20 g of 5-fluoro-l,3-dihydro-l-hydroxy-2,l-benzoxaborole (21 .2 mmol) and 3.20 g of ne glycol (51.6 mmol) are heated in 40 g of toluene. The toluene water azeotrope is led out of the system until the head temperature reached 110 oC. The toluene is removed Via rotary evaporator and the excess ethylene glycol is d by ohr lation at about torr and 100 CC bath temperature. Recrystallization from toluene tes 2.95 g of white ls, mp 145-149 c’C. Proton nmr shows spectra and integration consistent with the two to one product below: Example 2 — Preparation of Sample 2 3.00 g of l,3-dihydro-l-hydroxy-2,l-benzoxaborole (22.4 mmol) and 3.00 g of ethylene glycol (46.9 mmol) are heated in 40 g of toluene. The toluene water azeotrope is distilled out of the system until the head temperature reached 110 oC. The toluene is removed Via rotary evaporator and the excess ethylene glycol is removed by kugelrohr distillation at about torr and 100 CC bath temperature. Recrystallization from toluene generates 2.49 g of white crystals, mp 118 — 120.5 c’C. Proton NMR shows spectra and integration consistent with the two to one product.

Example 3 — Preparation of Sample 3 3.17 g of S-fluoro-l,3-dihydrohydroxy-2,1-benzoxaborole (21.0 mmol) and 3.22 g of pinacol (27.3 mmol) are heated in 40 g of e. The toluene water azeotrope is distilled out of the system until the head ature reached 110 oC. The toluene is removed via rotary evaporator and the excess l is d by ohr distillation at about 20 torr and 120 CC bath temperature. Recrystallization from hexane generatese 3.21 g of white crystals, mp 81- 89 OC. Proton NMR shows spectra and integration consistent with the two to one product. e 4 — Preparation of Sample 4 3.0 g of S-fluoro-l,3-dihydrohydroxy-2,1-benzoxaborole (19.9 mmol) and 2.5 g of 0panediol (propylene glycol; 32.9 mmol) are heated in 40 g of toluene. The e water azeotrope is distilled out of the system until the head temperature reached 110 CC. The toluene is removed via rotary ator and the excess propylene glycol is removed by kugelrohr distillation at about 20 torr and 110 CC bath temperature. Recrystallization from hexane generates 3.49 g of white crystals, mp 65.5-68.5 oC. Proton NMR shows spectra and integration consistent with the two to one product.

Example 5 - In Vitro Analysis 12-well (7 ml volume per well) microtiter plates are used for the in vitro inhibition assay for volatile antimicrobial compounds. A 3-ml volume of full-strength Potato Dextrose Agar (PDA) is added to each well. After cooling, 1 [LL of l X 106 per ml Botrytis cinerea spore suspension is spot pipette to the centre of the agar. For the first experiment, inoculated plates are allowed to germinate for 5 days at 4°C. For the second experiment, plates are inoculated immediately prior to le fungicide treatment. Small Whatman #1 filter disks (Cat. No. 1001-0155) are placed, in duplicate, on the underside of a polyethylene PCR plate sealing film.

For determination of the minimum inhibitory concentration (MIC), test compounds are diluted in acetone, and the appropriate amount of compound is added to disks in a dose dependent manner (1.25 to 0.0006 mg/disk).

Table 1. Antimicrobial activities ofMIScamples 1-4 The acetone is permitted to evaporate for 5 minutes. The headspace around the is a inoculum is then sealed inside the well by the film with the adhering disk containing the fungicide. Plates are inverted, placed over the treated disks and sealed to prevent any of the chemical from flakin from the disk and falling onto the inoculated agar. After 14 days of storage at 4 °C, cultures are ted for percent growth relative to control. Regardless of whether the spores had germinated for 5 days, or if the ent commenced soon after inoculation of the plates (~15 minutes); there is 100% control of the fungal pathogen down to 0.005 mg. Samples 1-4 show good antimicrobial activity against Botrytz's and/or other pathogens in this in vitro analysis. Minimum inhibitory concentrations (MIC) are shown in Tables 1 and 2 for results from two te tests.

Table 2. Antimicrobial activities ofMIScamples 1-4 (repeat test) Example 6 — Grape In Vivo Analysis In order to assess the in viva activity of volatile antimicrobial compounds, a volatile bioassay is ped using green table grape. Fruit are placed individually inside a 20 ml scintillation vial, with the stem wound facing upwards. The fresh stem wound is inoculated with uL of l X 106 per ml Botrytis cinerea spore suspension. Whatman filter paper (Cat. No. 1822-024) is placed inside duplicate vial caps. For determination of the MIC, test nds are diluted in acetone, and the appropriate amount of compound is added to disks in a dose dependent manner (for example 2.5 to 0.0024 mg/disk). The acetone is permitted to evaporate for 5 minutes. The vials are then capped with the lids containing the fiJngicide, and placed for 14 days at 4 °C. After storage, fruit are evaluated for incidence of e and appearance of phytotoxicity. Samples 1-4 show good antimicrobial activity against Botrytz's in this in vivo analysis.

Example 7 — Strawberry In Vivo Analysis In order to assess the in viva activity of volatile antimicrobial compounds, a volatile bioassay is developed using strawberry. Two fruit are placed inside a 240 ml jar, with the calyx facing downwards. A fresh wound is inoculated with 20 uL of l X 106 per ml Botrytis cinerea spore suspension. n filter paper (Cat. No. 1822-024) is placed inside duplicate jar lids.

For determination of the MIC, test compounds are d in acetone, and the appropriate amount of compound is added to disks in a dose dependent manner (for example 2.5 to 0.005 mg/disk).

The acetone is permitted to evaporate for 5 minutes. The jars are then capped with the lids containing the fungicide, and placed for 5 days at 21 °C. After e, fruit are evaluated for nce and severity of disease and appearance of phytotoxicity. s 1-4 show good antimicrobial activity against Botrytz's in this in vivo analysis.

Example 8 - Additional Strawberry In Vivo Analysis In order to assess the in viva dose by time activity of volatile antimicrobial nds, a volatile bioassay is developed using strawberry. Two fruit are placed inside a 240 ml jar, with the calyx facing downwards. A fresh wound is inoculated with 20 uL of l X 106 per ml Botrytis cinerea spore sion. Whatman filter paper (Cat. No. 1822-024) is placed inside ate jar lids. Test samples are diluted in acetone, and the appropriate amount of compound is added to disks for example at two rates 0.008 or 0.125 mg. The e is permitted to evaporate for 5 s. The jars are capped with the lids containing the fiJngicide, and ted with the volatile fungicide for l, 3, 6, 24 or 72 hours. After incubation, lids containing the disk with test compounds are replaced with new lids without test compounds. All samples are maintained at 21 °C for 3 days, then lids are removed and maintained for an additional 48 hours, all at 90% RH. Fruit are evaluated for incidence and severity of disease and appearance of oxicity. Samples 1-4 show good antimicrobial activity against is in this in viva analysis. e 9 — Antimicrobial Activity Against Bacteria ] 12-well (7 ml volume per well) microtiter plates are used for the in vitro inhibition assay for volatile antimicrobial compounds. A 3-ml volume of full-strength LB Agar is added to each well. After cooling, 15 uL ofEscherichia coli, adjusted to an optical density of 0.02 to 0.035, and further diluted 1/ 10 is pipette to the centre of the agar and tilted to distribute uniformly. Small Whatman #1 filter disks (Cat. No. 155) are placed, in duplicate, on the underside of a polyethylene PCR plate sealing film. For determination of the minimum inhibitory concentration (MIC), test compounds are diluted in acetone, and 5 mg of compound is added to disks. The acetone is permitted to evaporate for 5 minutes. The headspace around the Escherichia coli inoculum is then sealed inside the well by the film with the adhering disk containing the fungicide. Plates are inverted, placed over the treated disks and sealed to prevent any of the chemical from flaking from the disk and falling onto the inoculated agar. After 3 days of storage at 4 °C, cultures are erred to 23 °C for an additional 2 days, and then evaluated for colony growth relative to control. Samples 1-4 show good antimicrobial actiVity against Escherichia coli in this in vitro analysis. 1003290302

Claims (20)

The claims defining the invention are as s:

1. A compound having a structure of formula (A): RA – LA – G – LB – RB (A) each of RA and RB is independently derived from a member selected from the group consisting of 5-fluoro-1,3-dihydrohydroxy-2,1-benzoxaborole; 5-chloro-1,3-dihydro- oxy-2,1-benzoxaborole; 1,3-dihydrohydroxy-2,1-benzoxaborole; and combinations thereof; the – LA – G – LB – portion of formula (A) is derived from a diol or diamine compound; the diol compound is selected from the group consisting of 1,2-ethylene glycol; 1,2- propylene ; 1,3-propylene glycol; 1,1,2,2-tetramethyl-1,2-ethylene glycol; 2,2- yl-1,3-propylene glycol; 1,6-hexanediol; 1,10-decanediol; and combinations thereof; and the diamine compound is 1,2-ethylene diamine; 1,3-propylene diamine; or combinations f; G is a substituted or unsubstituted C1-8 -alkylene; and agriculturally acceptable salts thereof.

2. The compound of claim 1, wherein the compound is volatile.

3. The compound of claim 1 or 2, wherein the compound has antimicrobial activity.

4. The compound of any one of claims 1 to 3, wherein G is selected from –CH2–, –CH2– CH2–, –CH2C–CH2–CH2–, –CH(CH3)–CH2–, –C(CH3)2–C(CH3)2–, and –CH2–C(CH3)2– CH2–.

5. The compound of any one of claims 1 to 4, wherein each of RA and RB is independently F or . 1003290302

6. The compound of any one of claims 1 to 5, n the compound has the structure of

7. A method of using a compound against pathogens affecting meats, plants, or plant parts, comprising contacting the meats, plants, or plant parts with an effective amount of a compound having a ure of formula (A): RA – LA – G – LB – RB (A) wherein each of RA and RB is independently a l comprising an ole moiety is of formula (F) wherein A and D together with the carbon atoms to which they are attached form a 5, 6, or 7-membered fused ring which may be substituted by C1-6 -alkyl, C1-6 -alkoxy, hydroxy, halogen, nitro, nitrile, amino, amino substituted by one or more C1-6 -alkyl groups, carboxy, acyl, aryloxy, carbonamido, carbonamido substituted by C1-6 -alkyl, sulphonamido or trifluoromethyl or the fused ring may link two ole rings; B is boron; X1 is a group -CR7R8 wherein R7 and R8 are each independently hydrogen, C1-6 - alkyl, nitrile, nitro, aryl, aralkyl or R7 and R8 together with the carbon atom to which they are attached form an alicyclic ring; and 1003290302 each of LA and LB is independently –O–, , , or each of R and R’ is independently hydrogen, unsubstituted or tuted C1-18 -alkyl, arylalkyl, aryl, or heterocyclic moiety; and G is a tuted or unsubstituted C1-18 -alkylene, arylalkylene, arylene, or heterocyclic moiety; and lturally acceptable salts thereof.

8. The method of claim 7, wherein each of RA and RB is independently d from the group consisting of 5-fluoro-1,3-dihydrohydroxy-2,1-benzoxaborole; 5-chloro-1,3- dihydrohydroxy-2,1-benzoxaborole; 1,3-dihydrohydroxy-2,1-benzoxaborole; and combinations thereof.

9. The method of claim 7 or 8, wherein the – LA – G – LB – portion of formula (A) is derived from a diol or diamine compound.

10. The method of claim 9, wherein the diol compound is selected from the group ting of 1,2-ethylene glycol; 1,2-propylene glycol; 1,3-propylene glycol; 1,1,2,2-tetramethyl- 1,2-ethylene glycol; 2,2-dimethyl-1,3-propylene glycol; 1,6-hexanediol; 1,10-decanediol; and combinations thereof.

11. The method of claim 9, wherein the diamine compound is hylene diamine; 1,3- propylene diamine; or combinations thereof.

12. The method of any one of claims 7 to 11, n each of RA and RB is independently derived from a member selected from the group consisting of 5-fluoro-1,3-dihydro 1003290302 hydroxy-2,1-benzoxaborole; 5-chloro-1,3-dihydrohydroxy-2,1-benzoxaborole; 1,3- dihydrohydroxy-2,1-benzoxaborole; and ations thereof; the – LA – G – LB – portion of a (A) is derived from a diol or diamine compound; the diol compound is selected from the group consisting of 1,2-ethylene glycol; 1,2- propylene glycol; 1,3-propylene glycol; 1,1,2,2-tetramethyl-1,2-ethylene glycol; 2,2- dimethyl-1,3-propylene glycol; 1,6-hexanediol; 1,10-decanediol; and combinations thereof; and the diamine compound is 1,2-ethylene diamine; 1,3-propylene diamine; or combinations thereof; G is a substituted or unsubstituted C1-8 –alkylene; and agriculturally acceptable salts thereof.

13. The method of any one of claims 7 to 12, wherein G is selected from –CH2–, –CH2–CH2– , –CH2–CH2–CH2–, –CH(CH3)–CH2–, –C(CH3)2–C(CH3)2–, and –CH2–C(CH3)2–CH2–.

14. The method of any one of claims 7 to 13, wherein each of RA and RB is independently F or .

15. The method of any one of claims 7 to 14, wherein the compound has the ure of

16. The method of claim 7, n the compound has a structure of formula (A1) or (A2): 1003290302 (A1) (A2) n each of A1, A2, D1, and D2 is independently en, substituted or unsubstituted C1-18 -alkyl, arylalkyl, aryl, or heterocyclic; or A1 and D1, or A2 and D2 together form a 5, 6, or 7-membered fused ring which is substituted or unsubstituted; each of R16, R17, R18, and R19 is independently hydrogen, substituted or tituted C1-6 -alkyl, nitrile, nitro, aryl or aryl alkyl; or R16 and R17, or R18 and R19 together form an alicyclic ring which is substituted or unsubstituted; B is boron; and G is a substituted or unsubstituted C1-18 -alkylene, arylalkylene, arylene, or heterocyclic and lturally acceptable salts thereof.

17. The method of any one of claims 7 to 16, wherein the compound is volatile.

18. The method of any one of claims 7 to 17, wherein the compound is fungicide.

19. The method of any one of claims 7 to 18, wherein the meats, plants, or plant parts are selected from the group consisting of barley, camphor tree, canola, castor-oil plant, cinnamon, cocoa, coffee, corn, cotton, flax, grapevine, hemp, hops, jute, maize, mustard, 0302 nuts, oat, poppy, rape, rice, rubber plant, rye, sunflower, sorghum, soybean, sugar cane, tea, tobacco, and wheat.

20. The method of claim 7, wherein the plants are selected from the group ting of banana, pineapple, citrus, grapes, watermelon, cantaloupe, muskmelon, and other melons, apple, peach, pear, cherry, kiwifruit, mango, nectarine, guava, papaya, persimmon, pomegranate, avocado, fig, citrus, and berries.