Process of preparing etoposide phosphate and etoposide

US5459248A · kind A · utility

Assignee

• Bristol-Myers Squibb Company · US

Inventors

• Lee Jonathan Silverberg · Allentown, US
• Purushotham Vemishetti · East Syracuse, US
• John L. Dillon, Jr. · El Paso, US
• John J. Usher · East Syracuse, US

Key dates

• Filing date: Nov 4, 1993
• Grant date: Oct 17, 1995
• Expiry date: Nov 4, 2013

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Etoposide phosphate is prepared by coupling dibenzyl 4'-demethyl-4-epipodophyllotoxin-4'-phosphate with 2,3-di-O-benzyl-4,6-O-ethylidene-.alpha.,.beta.-D-glucopyranose in a solvent and subsequently removing the protecting groups. The tetra-benzyl protected etoposide phosphate is recrystallized from methanol or directly crystallized from acetonitrile by adding methanol to yield substantially the pure C-1"-.beta. form. The benzyl protecting groups are simultaneously removed by hydrogenation to produce etoposide phosphate in high yields. In a further embodiment, etoposide phosphate is treated with a phosphatase enzyme to yield etoposide.