Synthesis of desosamines

Patent metadata

Field	Value
Publication number	US-11008358-B2
Application number	US-201916724654-A
Country	US
Kind code	B2
Filing date	Dec 23, 2019
Priority date	Mar 25, 2015
Publication date	May 18, 2021
Grant date	May 18, 2021

Abstract

The present invention provides desosamine and mycaminose analogs and nitro sugars and methods for their preparation. The invention also provides methods of cyclizing a compound of Formula (A′) with glyoxal to give a nitro sugar of Formula (B). Methods for the preparation of compound of Formula (D′) are provided comprising cyclization of a nitro alcohol to give a nitro sugar and reduction and alkylation of the nitro sugar to give a desosamine, mycaminose, or an analog thereof.

First claim

What is claimed is:

1. A compound of Formula (J):

or salt thereof, wherein:
R 1a is —N(R S ) 2 , —NR S (OR S ), or of formula:

each of R 2a and R 3a is independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, or —OR SO ;
X S is a bond, —C(═O)—, —C(═NR SN )—, —S(═O)—, or —S(═O) 2 —;
L S2 is a bond, —NR S —, —O—, or —S—, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, and optionally substituted heteroalkynylene, and combinations thereof;
each R S is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or a sulfur protecting group when attached to a sulfur atom, or two R S attached to the same nitrogen atom are taken together to form ═N 2 or an optionally substituted heterocyclyl or heteroaryl ring;
each of R 7a and R 8a is independently optionally substituted C 1 -C 6 alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted acyl, or a nitrogen protecting group, or R 7a and R 8a are joined to form an optionally substituted heterocyclyl or heteroaryl ring;
each R SN is independently hydrogen, optionally substituted C 1 -C 6 alkyl, or a nitrogen protecting group, or two R SN attached to the same nitrogen atom are joined to form an optionally substituted heterocyclyl or heteroaryl ring;
each of R 4a and R 4b is independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, or —OR SO ; and
each of R 5 , R 6 and R SO is independently hydrogen, optionally substituted C 1 -C 6 alkyl, a carbohydrate, or an oxygen protecting group;
provided R 1a is not:

2. The compound of claim 1 , wherein the compound is of Formula (J-1), (J-d-1), (J-m-1), or (J-m-1-A):

or salt thereof.

3. The compound of claim 1 , or salt thereof, wherein R 7a and R 8a are methyl.

4. The compound of claim 1 , or salt thereof, wherein R 2a is hydrogen or methyl.

5. The compound of claim 1 , or salt thereof, wherein R 1a is —N(R S ) 2 .

6. The compound of claim 5 , or salt thereof, wherein R 1a is:

7. The compound of claim 1 , or salt thereof, wherein R 1a is —NHC(═O)R S , —NHC(═O)OR S , or —NHC(═O)N(R S ) 2 .

8. The compound of claim 7 , or salt thereof, wherein R 1a is:

9. The compound of claim 1 , or salt thereof, wherein R 1a is —NHC(═NR SN )R S , —NHC(═NR SN )OR S , —NHC(═NR SN )N(R S ) 2 , or —NHS(═O) 2 R S .

10. The compound of claim 9 , or salt thereof, wherein R 1a is:

11. A compound of Formula (K):

or salt thereof, wherein:
R 1b is —N(R S ) 2 , —NR S (OR S ), or of formula:

each of R 2b and R 3b is independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, or —OR SO ;
X S is a bond, —C(═O)—, —C(═NR SN )—, —S(═O)—, or —S(═O) 2 —;
L S2 is a bond, —NR S —, —O—, or —S—, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, and optionally substituted heteroalkynylene, and combinations thereof;
each R S is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or a sulfur protecting group when attached to a sulfur atom, or two R S attached to the same nitrogen atom are taken together to form ═N 2 or an optionally substituted heterocyclyl or heteroaryl ring;
R SN is hydrogen, optionally substituted alkyl, or a nitrogen protecting group;
each of R 4a and R 4b is independently hydrogen, optionally substituted C 1 -C 6 alkyl, or —OR SO ; and
each of R 5 , R 6 and R SO is independently hydrogen, halogen, optionally substituted C 1 -C 6 alkyl, a carbohydrate, or an oxygen protecting group;
provided R 1b is not:

12. The compound of claim 11 , wherein the compound is of Formula (K-1), (K-d-1), (K-m-1), (K-m-1-A):

or salt thereof.

13. The compound of claim 11 , or salt thereof, wherein R 2b is hydrogen or methyl.

14. The compound of claim 11 , or salt thereof, wherein R 1b is —N(R S ) 2 .

15. The compound of claim 14 , or salt thereof, wherein R 1b is:

16. The compound of claim 11 , or salt thereof, wherein R 1b is —NHC(═O)R S , —NHC(═O)OR S , or —NHC(═O)N(R S ) 2 .

17. The compound of claim 16 , or salt thereof, wherein R 1b is:

18. The compound of claim 11 , or salt thereof, wherein R 1b is —NHC(═NR SN )R S , —NHC(═NR SN )OR S , or —NHC(═NR SN )N(R S ) 2 .

19. The compound of claim 11 , or salt thereof, wherein R 1b is —NHS(═O) 2 R S .

20. The compound of claim 11 , or salt thereof, wherein R 1b is:

Assignees

• Harvard College

Inventors

• Myers Andrew G
• Zhang Ziyang

Classifications

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07H15/12 Primary

  attached to a nitrogen atom of the saccharide radical · CPC title

• C07C201/12

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

• C07H15/18

  Acyclic radicals, substituted by carbocyclic rings · CPC title