Methods and compositions for terpenoid tricycloalkane synthesis

Patent metadata

Field	Value
Publication number	US-11485704-B2
Application number	US-202117183978-A
Country	US
Kind code	B2
Filing date	Feb 24, 2021
Priority date	May 16, 2018
Publication date	Nov 1, 2022
Grant date	Nov 1, 2022

Abstract

In one aspect, the disclosure relates to methods for preparation of intermediates useful for the preparation of terpenoid cores. In a further aspect, the disclosed methods pertain to the preparation of compounds comprising a terpenoid core or scaffold, such as 6/7/5 tricycloalkanes. The disclosed methods utilize abundant starting materials and simple reaction sequences that can be used to tunably and scalably assemble common terpenoid cores. In various aspects, the present disclosure pertains to compounds prepared using the disclosed methods. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

First claim

What is claimed is:

1. A compound, wherein the compound has a formula represented by a structure:

wherein E is —(C═O)OR 10 , wherein R 10 is C1-C6 alkyl;
wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) m (C═O)OR 11 ; or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 —, or —CH═CH—, wherein m is an integer selected from 0, 1, 2, and 3; and wherein R 11 is C1-C6 alkyl;
wherein R 2 is hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) n (C═O)OR 12 , wherein n is an integer selected from 0, 1, 2, and 3; and wherein R 12 is C1-C6 alkyl;
wherein A 1 is —C(R 20 ) (R 21 )—, wherein R 20 is C1-C6 alkyl, or —(CH 2 ) p C═O)OR 30 , wherein R 30 is C1-C6 alkyl, wherein p is an integer selected from 0, 1, 2, and 3, wherein R 21 is hydrogen, C1-C6 alkyl, or —(CH 2 ) q C═O)OR 31 , wherein R 31 is C1-C6 alkyl, and wherein q is an integer selected from 0, 1, 2, and 3.

2. The compound of claim 1 , wherein E is —(C═O)OCH 3 .

3. The compound of claim 1 , wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, methyl, phenyl, or —CH 2 (C═O)OCH 3 .

4. The compound of claim 1 , wherein each of R 1b and R 1c are hydrogen; or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 — or —CH═CH—.

5. The compound of claim 1 , wherein R 2 is hydrogen, methyl, phenyl, or —(CH 2 )(C═O)OCH 3 .

6. The compound of claim 1 wherein A 1 is —CHCH 3 , or —CH (C═O)OCH 2 CH 3 .

7. A compound, wherein the compound has a formula represented by a structure:

wherein E is —CN or —(C═O)OR 10 ;
wherein R 10 is C1-C6 alkyl;

wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) m (C═O)OR 11 , or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 —, or —CH═CH—, wherein m is an integer selected from 0, 1, 2, and 3, and wherein R 11 is C1-C6 alkyl;
wherein R 2 is hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) n (C═O)OR 12 , wherein n is an integer selected from 0, 1, 2, and 3, and wherein R 12 is C1-C6 alkyl;
wherein A 1 is —NR 22 —, wherein R 22 is C1-C6 alkyl, or —(C═O)OR 32 ; and
wherein R 32 is C1-C6 alkyl.

8. The compound of claim 7 , wherein E is —CN or —(C═O)OCH 3 .

9. The compound of claim 7 , wherein E is —CN.

10. The compound of claim 7 , wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, methyl, phenyl, or —CH 2 (C═O)OCH 3 .

11. The compound of claim 7 , wherein each of R 1b and R 1c are hydrogen; or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 — or —CH═CH—.

12. The compound of claim 7 , wherein R 2 is hydrogen, methyl, phenyl, or —CH 2 (C═O)OCH 3 .

13. The compound of claim 7 , wherein A 1 is —N(C═O)OC(CH 3 ) 3 .

14. A compound, wherein the compound has a formula represented by a structure:

wherein E is —(C═O)OR 10 , wherein R 10 is C1-C6 alkyl;
wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) m (C═O)OR 11 ; or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 —, or —CH═CH—, wherein m is an integer selected from 0, 1, 2, and 3; and wherein R 11 is C1-C6 alkyl;
wherein R 2 is hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) n (C═O)OR 12 , wherein n is an integer selected from 0, 1, 2, and 3, and wherein R 12 is C1-C6 alkyl;
wherein A 1 is —C(R 20 )(R 21 )—, —NR 22 — or —CH 2 —, wherein R 20 and R 21 are each independently selected from: hydrogen, C1-C6 alkyl, or —(CH 2 ) p C═O)OR 30 ; wherein R 30 is C1-C6 alkyl; and wherein p is an integer selected from 0, 1, 2, and 3; and wherein R 22 is C1-C6 alkyl, or —(C═O)OR 32 ; and wherein R 32 is C1-C6 alkyl.

15. A compound, wherein the compound has a formula represented by a structure:

wherein E is —CN or —(C═O)OR 10 , wherein R 10 is C1-C6 alkyl;
wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) m (C═O)OR 11 ; or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 —, or —CH═CH—, wherein m is an integer selected from 0, 1, 2, and 3; and wherein R 11 is C1-C6 alkyl;
wherein R 2 is C1-C6 alkyl, aryl, or —(CH 2 ) n (C═O)OR 12 , wherein n is an integer selected from 0, 1, 2, and 3, and wherein R 12 is C1-C6 alkyl;
wherein A 1 is —C(R 20 )(R 21 )—, —NR 22 — or —CH 2 —, wherein R 20 and R 21 are each independently selected from: hydrogen, C1-C6 alkyl, or —(CH 2 ) p C═O)OR 30 ; wherein R 30 is C1-C6 alkyl, wherein if R 20 or R 21 are H, only one of R 20 and R 21 is H; and wherein p is an integer selected from 0, 1, 2, and 3; and wherein R 22 is C1-C6 alkyl, or —(C═O)OR 32 ; and wherein R 32 is C1-C6 alkyl.

16. A compound, wherein the compound has a formula represented by a structure:

wherein E is —CN or —(C═O)OR 10 , wherein R 10 is C1-C6 alkyl;
wherein each of R 1a , R 1b , R 1c , and R 1d is independently hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) m (C═O)OR 11 ; or wherein R 1a and R 1c are covalently bonded and, together with more intermediate carbons, comprise —CH 2 CH 2 —, or —CH═CH—, wherein at least one of R 1a , R 1b , R 1c , and R 1d is not hydrogen, wherein m is an integer selected from 0, 1, 2, and 3; and wherein R 11 is C1-C6 alkyl;
wherein R 2 is hydrogen, C1-C6 alkyl, aryl, or —(CH 2 ) n (C═O)OR 12 , wherein n is an integer selected from 0, 1, 2, and 3, and wherein R 12 is C1-C6 alkyl;
wherein A 1 is —C(R 20 )(R 21 )—, —NR 22 — or —CH 2 —, wherein R 20 and R 21 are each independently selected from: hydrogen, C1-C6 alkyl, or —(CH 2 ) p C═O)OR 30 ;
wherein R 30 is C1-C6 alkyl, wherein if R 20 or R 21 are H, only one of R 20 and R 21 is H; and wherein p is an integer selected from 0, 1, 2, and 3; and wherein R 22 is C1-C6 alkyl, or —(C═O)OR 32 ; and wherein R 32 is C1-C6 alkyl.

17. The compound of claim 14 , wherein A 1 is —CHCH 3 , —CH(C═O)OCH 2 CH 3 , or —N(C═O)OC(CH 3 ) 3 .

Assignees

• Univ Florida

Inventors

• Grenning Alexander James
• Scott Sarah

Classifications

• C07C255/31

  having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing rings other than six-membered aromatic rings · CPC title

• C07C255/47

  to carbon atoms of rings being part of condensed ring systems · CPC title

• C07D227/04

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms · CPC title

• C07C253/30 Primary

  by reactions not involving the formation of cyano groups · CPC title

• C07C2603/78

  containing seven-membered rings · CPC title