Regioselective and stereoselective oxidation of fused ring systems useful for the preparation of aminosterols
AssigneeGenaera Corporation
InventorsWilliam A. Kinney, Xuehai Zhang, Ronald Michalak
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Abstract
An efficient method for the synthesis of aminosterol compounds such as squalamine and compound 1436 is described. A method of the invention provides for regioselective oxidation and regioselective sulfonation of a fused ring system. The fused ring base can be, for example, a steroid ring base. The aminosterol compounds are effective as, for example, antibiotics, antiangiogenic agents and NHE3 inhibitors.
Claims15
A method for regioselectively oxidizing a primary hydroxyl substituent attached to a fused ring base in the presence of a secondary hydroxyl substituent attached to said fused ring base comprising the step of:
- reacting a fused ring system comprising a primary hydroxyl substituent and a secondary hydroxyl substituent with bleach in the presence of a catalyst wherein solely said primary hydroxyl substituent is oxidized to an aldehyde.
A method for regioselectively sulfonating a first secondary hydroxyl substituent attached to a fused ring base in the presence of a second secondary hydroxyl substituent attached to said fused ring base comprising the step of:
- reacting a fused ring system comprising a first secondary hydroxyl substituent and a second secondary hydroxyl substituent with a sulfur trioxide-pyridine complex to regioselectively sulfonate said first secondary hydroxy substituent.
A method for preparing an aminosterol compound comprising the steps of:
- (a) reacting compound 2:
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- under conditions sufficient to form compound 3:
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- (b) reacting compound 3 under conditions sufficient to form compound 4:
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- (c) reacting compound 4 under conditions sufficient to form compound 5:
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- (d) reacting compound 5 under conditions sufficient to form compound 7:
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- (e) reacting compound 7 under conditions sufficient to form compound 8:
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- (f) reacting compound 8 under conditions sufficient to form compound 9:
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- (g) reacting compound 9 under conditions sufficient to form compound 10:
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- (h) reacting compound 10 under conditions sufficient to form compound 11:
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- (i) reacting compound 11 under conditions sufficient to form an aminosterol compound of the general formula:
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- where NR1R2 forms a saturated or unsaturated, linear or branched amino group.
A compound selected from the group consisting of:
- 35 36
Dependencies are inferred from the claim text.