Alla P Kucherenko

US Patent:

60432713, Mar 28, 2000

Filed:

Aug 2, 1995

Appl. No.:

8/510213

Inventors:

Michael T. Flavin - Darien IL
Ze-Qi Xu - Naperville IL
John D. Rizzo - Downers Grove IL
Alla Kucherenko - Naperville IL
Albert Khilevich - Glenview IL
Abram Kivovich Sheinkman - Naperville IL
Vilayphone Vilaychack - Elgin IL
Lin Lin - Chicago IL
Wei Chen - Naperville IL
William A. Boulanger - Schenectady NY

Assignee:

Sarawak MediChem Pharmaceuticals, Inc. - Lemont IL

International Classification:

A61K 3135
C07D40700

US Classification:

514453

Abstract:

A method of preparing (. +-. )-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (. +-. )-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (. +-. )-calanolide A. A method for resolving (. +-. )-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing a viral infections using (. +-.

US Patent:

58693246, Feb 9, 1999

Filed:

Sep 8, 1997

Appl. No.:

8/933619

Inventors:

Michael T. Flavin - Darien IL
Ze-Qi Xu - Naperville IL
John D. Rizzo - Downers Grove IL
Alla Kucherenko - Naperville IL
Albert Khilevich - Glenview IL
Abram Kivovich Sheinkman - Naperville IL
Vilayphone Vilaychack - Elgin IL
Lin Lin - Chicago IL
Wei Chen - Naperville IL
William A. Boulanger - Schenectady NY

Assignee:

Sarawak MediChem Pharmaceuticals, Inc. - Lemont IL

International Classification:

C12P 4100

US Classification:

435280

Abstract:

A method of preparing (. +-. )-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (. +-. )-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (. +-. )-calanolide A. A method for resolving (. +-. )-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing viral infections using (. +-.