Olfactory ligands

Patent metadata

Field	Value
Publication number	US-2018271089-A1
Application number	US-201515542097-A
Country	US
Kind code	A1
Filing date	Dec 23, 2015
Priority date	Jan 9, 2015
Publication date	Sep 27, 2018
Grant date	—

Abstract

The invention provides analogues of (S)-germacrene D analogue which have improved insect repellent properties compared to (S)-germacrene D analogue or which have insect attractant properties.

First claim

1 . A (S)-germacrene D analogue of general formula (I):

wherein
R 1 is H, methyl, ethyl, n-propyl, iso-propyl or cyclopropyl;
R 2 is H, methyl, ethyl, n-propyl, iso-propyl or cyclopropyl;
R 3 is methyl, ethyl, n-propyl, iso-propyl or cyclopropyl;
R 4 is H, methyl, ethyl, n-propyl, iso-propyl or cyclopropyl;
R 5 is H, methyl, ethyl, n-propyl, iso-propyl or cyclopropyl.

2 . The compound according to claim 1 wherein, independently or in any combination:
R 1 is H, methyl or ethyl;
R 2 is H, methyl or ethyl;
R 3 is methyl or ethyl;
R 4 is H, methyl or ethyl;
R 5 is H, methyl or ethyl.

3 . The compound according to claim 1 wherein:
each of R 1 , R 2 and R 4 is H;
R 3 is methyl, ethyl, n-propyl, iso-propyl or cyclopropyl; and
R 5 is H, methyl, ethyl, n-propyl, iso-propyl or cyclopropyl.

4 . The compound according to claim 3 wherein R 5 is H.

5 . The compound according to claim 4 which is (S)-15-methylgermacrene D.

6 . The compound according to claim 1 wherein each of R 2 , R 3 and R 5 is independently methyl, ethyl, n-propyl, iso-propyl or cyclopropyl and each of R 1 and R 4 is H;

7 . The compound according to claim 6 wherein R 5 is H.

8 . The compound according to claim 7 which is ((S)-14,15-dimethylgermacrene D.

9 . The process for the preparation of a compound according to claim 1 , the process comprising incubating a farnesyl diphosphate analogue of general formula (II):

wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in general formula (I);
or a salt thereof;
with germacrene D synthase (GDS).

10 . The process according to claim 9 wherein the germacrene D synthase is a recombinant (S)-germacrene D synthase polypeptide.

11 . The process according to claim 10 wherein the recombinant GDS comprises a tag sequence at the N- or C-terminus, in particular a polyhistidine tag.

12 . The process according to claim 11 wherein the GDS comprises a C-terminal polyhistidine tag, for example a hexahistidine tag.

13 . The process according to claim 9 wherein the GDS is native germacrene D synthase from Solidago canadensis SEQ ID NO: 1.

14 . The process according to claim 9 wherein the GDS is native germacrene D synthase from Solidago canadensis SEQ ID NO: 1, which has one or more of the modifications:
tyrosine residue at position 406 replaced by phenylalanine, leucine, isoleucine, valine or alanine;
tryptophan residue at position 275 replaced by phenylalanine, leucine, isoleucine, valine or alanine, but especially by phenylalanine;
tyrosine residue at position 524 replaced by phenylalanine, leucine, isoleucine, valine or alanine, but especially by phenylalanine.

15 . The process according to claim 14 wherein the GDS has one or more of tyrosine at position 406, tryptophan at position 275 tyrosine at position 524 replaced by phenylalanine.

16 . A modified GDS polypeptide comprising a native germacrene D synthase from Solidago canadensis SEQ ID NO: 1, which has one or more of the modifications:
tyrosine residue at position 406 replaced by phenylalanine, leucine, isoleucine, valine or alanine; tryptophan residue at position 275 replaced by phenylalanine, leucine, isoleucine, valine or alanine, but especially by phenylalanine; tyrosine residue at position 524 replaced by phenylalanine, leucine, isoleucine, valine or alanine, but especially by phenylalanine.

17 . The modified GDS polypeptide according to claim 16 wherein the GDS has one or more of tyrosine at position 406, tryptophan at position 275 tyrosine at position 524 replaced by phenylalanine.

18 . A nucleic acid sequence encoding the modified GDS polypeptide according to claim 16 .

19 . A vector comprising the nucleic acid sequence according to claim 18 .

20 . A cell transfected or transformed with the nucleic acid molecule according to claim 18 .

21 . An insect repellent composition comprising the compound according to claim 1 and a suitable carrier, provided that the compound of general formula (I) is not (S)-14,15-dimethylgermacrene D.

22 . The insect repellent composition according to claim 21 including the compound of general formula (I) wherein:
each of R 1 , R 2 and R 4 is H;
R 3 is methyl, ethyl, n-propyl, iso-propyl or cyclopropyl; and
R 5 is H, methyl, ethyl, n-propyl, iso-propyl or cyclopropyl.

23 . The insect repellent composition according to claim 21 further comprising one or more addition insect repelling compounds selected from the group consisting of allethrins, DEET (N,N-diethyl-m-toluamide), p-menthane-3,8-diol (PMD), picaridin, Bayrepel, KBR 3023, Nepetalactone, Citronella oil, Neem oil, Bog Myrtle, Dimethyl carbate, Tricyclodecenyl allyl ether, IR3535 (3-[N-Butyl-N-acetyl]-aminopropionic acid, ethyl ester) or anthranilate-based insect repellents.

24 . The insect repellent composition according to claim 21 comprising a carrier suitable for application to human or animals.

25 . An insect attractant composition comprising a compound according to claim 1 and a suitable carrier, provided that the compound is not (S)-15-methylgermacrene D.

26 . The insect attractant composition according to claim 25 wherein the compound of general formula (I) is (S)-14,15-dimethylgermacrene D.

27 . The insect attractant composition according to claim 25 further comprising an insecticide.

28 . The insect attractant composition according to claim 25 further comprising a controlled release medium selected from the group consisting of rubber, polythene, hollow fibres, plastic sandwiches, plastic membranes and cellulosic materials, so that the attractant is released over a period of days at a concentration effective to attract insects.

29 . An insect trapping device comprising an insect attractant composition according to claim 25 .

30 . (canceled)

31 . A method of repelling insects comprising providing an insect repellent composition according to claim 21 in an area affected by insect infestation.

32 . A method of attracting insects comprising providing an insect attractant composition according to claim 25 in an area affected by insect infestation.

33 . A cell transfected or transformed with the vector according to claim 19 .

Assignees

• Univ College Cardiff Consultants Ltd
• Rothamsted Res

Inventors

• Pickett John Anthony
• Birkett Michael Alexander
• Miller David James
• Allemann Rudolf Konrad

Classifications

• C07C2601/18

  with a ring being at least seven-membered · CPC title

• C12P5/002

  cyclic (compounds containing at least three condensed carbocyclic rings C12P15/00) · CPC title

• C07C13/271

  with a nine- to ten- membered ring · CPC title

• C12N9/88

  Lyases (4.) · CPC title

• A01N27/00 Primary

  Biocides, pest repellants or attractants, or plant growth regulators containing hydrocarbons · CPC title