# US 5,710,259 A · Oligosaccharide-containing 14-aminosteroid compounds and novel diastereoselective aminosteroid process chemistry

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- Number: US 5,710,259 A
- Document ID: US5710259A
- Status: Granted
- Kind: A
- Application number: 08/459,911
- Filed: 1995-06-02
- Granted: 1998-01-20
- Earliest claimed: 1993-09-24
- Assignees: The Procter & Gamble Company
- Inventors: Paul Michael Dybas; Roland Norman Johnson; Randy Stuart Muth; Song Liu
- Web page: https://patentgrep.com/patent/US5710259A

## CPC

- C07J 41/0011: {Unsubstituted amino radicals}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- C07J 3/005: {the carbon atom being part of a carboxylic function}
- C07J 17/005: {Glycosides}
- C07J 19/005: {Glycosides}
- C07J 41/00: Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J 41/0038: {with an androstane skeleton, including 18- or 19-substituted derivatives, 18-nor derivatives and also derivatives where position 17-beta is substituted by a carbon atom not directly bonded to a further carbon atom and not being part of an amide group}
- C07J: STEROIDS (seco-steroids C07C)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to oligosaccharide-containing 14-aminosteroid compounds and the pharmaceutically-acceptable acid salts or esters thereof of the general formula: ##STR1## wherein a) R.sub.1 is (i) COOR.sub.5, where R.sub.5 is hydrogen, a 1-6 carbon lower alkyl; a 1-6 carbon lower alkyl substituted by an amino group; an arylalkyl or heteroarylalkyl or a carbocyclic ring, or (ii) CHR.sub.6 OH, where R.sub.6 is a hydrogen atom or 1-6 carbon lower alkyl group, or (iii) COR'", where R'" is hydrogen; 1-6 carbon lower alkyl; 1-6 carbon lower alkyl substituted amino; amino or dialkylamino; and b) R.sub.2 is --NR.sub.7 R.sub.8, where R.sub.7 and R.sub.8, which may be the same or different, are hydrogen atoms or a 1-6 carbon lower alkyl; and c) R.sub.3 is an oligosaccharide sugar residue; and d) R.sub.4 is (i) OH, or (ii) H, or (iii) OR.sub.13, where R.sub.13 is a monosaccharide sugar residue; acetoxy; benzoxy; arylalkyl or heteroarylalkyl; and e) Z is (i) --CH--, where a and b are single bonds, or (ii) .dbd.C, where either a or b is a double bond. The present invention also relates to a process for introducing an amino group at the 14-position on a steroid nucleus wherein said amino group is diasteroselectively introduced onto the 14-position of the steroid nucleus via an iodoisocyanate addition comprising the steps of: a) adding the iodoisocyanate to the 14-15 position double bond on the steroid nucleus; and b) dehalogenation; and c) isocyanate conversion to the amine moiety on the 14-position of the steroid nucleus.

## Claims

### Claim 1

A process for introducing an amino group at the 14-position on asteroid nucleus, wherein said amino group is diasteroselectively introduced onto the 14-position of the steroid nucleus via an iodoisocyanate addition comprising the steps of:
a) adding the iodoisocyanate to the 14-15 position double bond on the steroid nucleus; and
b) dehalogenation; and
c) isocyanate conversion to the amine moiety on the 14-position of the steroid nucleus.

### Claim 2 (depends on 1)

A process according to claim 1, wherein said iodoisocyanate addition is accomplished using silver cyanate and iodine.

### Claim 3 (depends on 1)

A process according to claim 1, wherein said dehalogenation is accomplished using alkyltin hydrides and radical initiators.

### Claim 4 (depends on 3)

A process according to claim 3, wherein said alkyltin hydride is tri-n-butyltin hydride and said radical initiator is benzoyl peroxide.

### Claim 5 (depends on 1)

A process according to claim 1, wherein the isocyanate conversion to the amine moiety is via aqueous hydrolysis.

### Claim 6 (depends on 5)

A process according to claim 5, wherein said hydrolysis is via the addition of hydrochloric acid.

### Claim 7 (depends on 5)

A process according to claim 5, wherein said hydrolysis is via the addition of potassium carbonate.

### Claim 8 (depends on 1)

A process according to claim 1 wherein adding the iodoisocyanate is at a temperature of from about -30.degree. C. to about 100.degree. C.

### Claim 9 (depends on 1)

A process according to claim 1 wherein the iodoisocyanate step has a reaction time of from about 1 to about 6 hours.

### Claim 10 (depends on 5)

A process according to claim 5 wherein adding the iodoisocyanate is at a temperature of from about -30.degree. C. to about 100.degree. C.

### Claim 11 (depends on 5)

A process according to claim 5 wherein the iodoisocyanate step has a reaction time of from about 1 to about 6 hours.

### Claim 12 (depends on 1)

A process for the preparation of an oligosaccharide containing 14-aminosteroid compound according to claim 1, wherein the amino group on the 14-position of the steroid nucleus is diasteroselectively introduced onto the 14-position of the steroid nucleus via an iodoisocyanate addition comprising the steps of:
a) reacting silver cyanate and iodine at a temperature from about -30.degree. C. to 100.degree. C. for about 1 to about 6 hours to generate iodoisocyanate to the 14-15 position double bond on the steroid nucleus; and
b) dehalogenating at a temperature from about 0.degree. C. to about 100.degree. C. for about 1 to about 6 hours; and
c) hydrolyzing the isocyanate group to the amine moiety on the 14-position of the steroid nucleus at a temperature from about 0.degree. C. to about 60.degree. C. for about 2 to about 72 hours.