Amino polyols and amino sugars

• US 20040053330A1
• Filed: 04/01/2003
• Published: 03/18/2004
• Est. Priority Date: 06/28/1996
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Petasis, Nicos A., Zavialov, Ilia A., Patel, Zubin D.
• Granted Patent: US 7,462,746 B2
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: B01J 2219/00738 Organic catalysts
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/00747 Catalysts
• CPC Class Codes: B01J 2531/824 Palladium
• CPC Class Codes: B01J 31/2409 with more than one complexing phosphine-P atom
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07C 213/02 by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
• CPC Class Codes: C07C 215/28 and containing six-membered aromatic rings
• CPC Class Codes: C07C 215/30 containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 215/50 with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• CPC Class Codes: C07C 227/10 with simultaneously increasing the number of carbon atoms in the carbon skeleton
• CPC Class Codes: C07C 229/36 with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 231/08 from amides by reaction at nitrogen atoms of carboxamide groups
• CPC Class Codes: C07C 233/47 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 2603/74 Adamantanes
• CPC Class Codes: C07D 207/16 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 295/15 to an acyclic saturated chain
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/16 by oxygen atoms
• CPC Class Codes: C07D 333/20 : by nitrogen atoms nitro, nitroso radicals C07D333/12
• CPC Class Codes: C07D 333/24 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/58 : Radicals substituted by nitrogen atoms
• CPC Class Codes: C07D 333/60 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07H 5/06 : Aminosugars
• CPC Class Codes: C40B 30/08 : by measuring catalytic activity
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials

Abstract

Synthetic methods provide for the simple, efficient preparation of amino polyols and derivatives. The methods include a three-component reaction of a carbohydrates with organoboron compounds and primary or secondary amine derivatives. The resulting amino polyols can be transformed into amino sugars. In one implementation, the amine moiety is protected, and an alkenyl, aryl or heteroaryl moiety is cleaved to form the amino sugar. Amino polyols and amino sugars prepared according to the methods are also described.

Claims

1. A method for preparing an amino polyol comprising:

providing a carbohydrate;

providing an amine;

providing an organoboron derivative; and

allowing the carbohydrate, amine and organoboron derivative to react to form an aminopolyol.

2. A method for preparing an amino polyol, the method comprising:

providing a carbohydrate of formula 1a or 1b

wherein;

n and m are integers from 0-4 and n is greater than or equal to m;

Ra is hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl, heteroaryl, acyl, carboxyalkyl, or carboxyaryl;

R¹ is hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl or heteroaryl; and

the Z substituents are independently selected from the group consisting of hydroxy, hydrogen, and —

OR, where R is alkyl, aryl, silyl, acyl, alkoxyacyl or aminoacyl, provided that Z can exist as an acetal or ketal and provided that at least one Z substituent in the carbohydrate of formula 1a or 1b must be hydroxy or —

OR;

providing an amine of formula 2

wherein;

R² and R³ are independently selected from the group consisting of hydrogen, alkyl, aryl, hydroxy, alkoxy, acyl, carboxyalkyl, carboxamido, alkylamino, dialkylamino, acylamino, silyl, phosphinyl, sulfonyl, sulfinyl, and alkylsulfonate, provided that R² and R³ can be joined together to form one or more rings of 2 to 20 atoms;

providing an organoboron derivative of formula 3

wherein;

R⁴ is alkenyl, alkynyl, allenyl, or aryl;

X and Y are independently selected from hydroxy, alkoxy, aryloxy, halo, amino, alkylamino, dialkylamino, alkyl or aryl, provided that the organoboron derivative can include a fourth boron substituent selected from hydroxy, alkoxy, dialkylamino and halo; and

allowing the carbohydrate, amine and organoboron derivative to react to form an amino polyol product of formula 4.

3. The method of claim 2, wherein the carbohydrate of formula 2, the amine of formula 2 or the organoboron compound of formula 3 is attached to a polymer or other solid support.

4. The method of claim 2 or claim 3, further comprising:

treating the aminopolyol product of formula 4 to form an amino sugar of formula 11a or 11b or formula 12a or 12b

wherein;

R⁶ and R⁷ are independently selected from the group consisting of hydrogen, acyl, alkoxyacyl, aminoacyl, carbamate, sulfonyl, sulfinyl, phosphonate and sulfonate, provided that R⁶ and R⁷ can be the same as substituents R² or R³and further provided that R⁶ and R⁷ can be joined together to form one or more rings;

R⁸is hydrogen, alkyl or acyl; and

R⁹is hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl, heteroaryl, acyl, carboxyalkyl, or carboxyaryl.

5. The method of claim 4, wherein:

treating the aminopolyol product includes forming a protected amine and treating the protected amine with a cleaving agent to generate a carbonyl group.

6. The method of claim 2, wherein the amino polyol is formed in predominantly one stereoisomer having the amino group in an anti-relationship to the adjacent hydroxyl group.

7. The method of claim 2, further comprising:

treating the amino polyol product to protect the amino group; and

oxidizing the polyol to generate a protected amino acid.

8. The method of claim 4, wherein one or more of R² or R³ is benzyl or substituted benzyl.

9. The method of claim 4, wherein the amine of formula 2 is 1,1-di(p-anisyl)methylamine.

10. The method of claim 4, wherein one or more of R² or R³ is allyl or substituted allyl.

11. The method of claim 4, wherein the amine of formula 2 is diallylamine.

13. A compound of formula 4,

15. A compound of formula 11a or 11b or formula 12a or 12b,

19. A compound prepared according to claim 4, selected from the group consisting of:

12. A compound of formula 4

14. A compound of formula 11a or 11b or formula 12a or 12b,

16. A compound selected from the group consisting of:

17. The compound of claim 16, wherein:

at least one of R² and R³ is not hydrogen or acyl.

18. The ammonium salt of a compound according to claim 16.

21. The method of claim 17, further comprising:

treating the aminopolyol product of formula 4 to form an amino sugar of formula 11a or 11b or formula 12a or 12b

wherein;

R⁶ and R⁷ are independently selected from the group consisting of hydrogen, acyl, alkoxyacyl, aminoacyl, carbamate, sulfonyl, sulfinyl, phosphonate and sulfonate, provided that R ⁶and R⁷ can be the same as substituents R² or R³ and further provided that R⁶ and R⁷ can be joined together to form one or more rings;

R⁸ is hydrogen, alkyl or acyl; and

R⁹ is hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl, heteroaryl, acyl, carboxyalkyl, or carboxyaryl.

25. The ammonium salt of a compound according to claim 17.

20. A method for preparing an amino polyol, the method comprising:

providing a carbohydrate derivative of formula 1a or 1b

wherein;

n and m are integers from 0-4 and n is greater than or equal to m;

Ra is hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl, heteroaryl, acyl, carboxyalkyl, or carboxyaryl;

R¹ is hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl or heteroaryl; and

the Z substituents are independently selected from the group consisting of hydroxy, hydrogen, alkyl, alkenyl, alkynyl, allenyl, aryl, heteroaryl, acyl, oxo, carboxy, carboxyalkyl, carboxyaryl, carboxamido, dialkylamino, acylamino, cyano, sulfonylamino, carbamate, acetal, ketal, borate, boronate, 3-7 membered heterocycle, and —

OR, where R is alkyl, aryl, heteroaryl, silyl, acyl, alkoxyacyl or aminoacyl, provided that at least one Z substituent in the carbohydrate of formula 1a or 1b must be hydroxy or —

OR and that at least one Z substituent is not hydrogen, hydroxy, acetal, ketal, or —

OR;

providing an amine of formula 2

wherein;

R² and R³ are independently selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, hydroxy, alkoxy, acyl, carboxyalkyl, carboxamido, alkylamino, dialkylamino, acylamino, silyl, phosphinyl, sulfonyl, sulfinyl, and alkylsulfonate, provided that R² and R³ can be joined together to form one or more rings of 2 to 20 atoms;

providing an organoboron derivative of formula 3

wherein;

R⁴ is alkenyl, alkynyl, allenyl, or aryl;

X and Y are independently selected from hydroxy, alkoxy, aryloxy, halo, amino, alkylamino, dialkylamino, alkyl or aryl, provided that the organoboron derivative can include a fourth boron substituent selected from hydroxy, alkoxy, dialkylamino and halo; and

allowing the carbohydrate, amine and organoboron derivative to react to form an amino polyol product of formula 4.

22. A compound of formula 4

23. A compound of formula 11a or 11b or formula 12a or 12b,

24. A compound selected from the group consisting of:

26. The ammonium salt of a compound according to claim 24.