Details

Autor(en) / Beteiligte

• Buckland, Barry C.
• Drew, Stephen W.
• Connors, Neal C.
• Chartrain, Michel M.
• Lee, Chanyong
• Salmon, Peter M.
• Gbewonyo, Kodzo
• Zhou, Weichang
• Gailliot, Pat
• Singhvi, Rahul
• Olewinski, Roger C.
• Sun, Wen-Jun
• Reddy, Jayanthi
• Zhang, Jinyou
• Jackey, Barbara A.
• Taylor, Colleen
• Goklen, Kent E.
• Junker, Beth
• Greasham, Randolph L.

Titel

Microbial Conversion of Indene to Indandiol: A Key Intermediate in the Synthesis of CRIXIVAN

Ist Teil von

• Metabolic engineering, 1999-01, Vol.1 (1), p.63-74

Ort / Verlag

Belgium: Elsevier Inc

Erscheinungsjahr

1999

Link zum Volltext

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Indene is oxidized to mixtures ofcis- andtrans-indandiols and related metabolites byPseudomonas putidaandRhodococcussp. isolates. Indene metabolism is consistent with monooxygenase and dioxygenase activity.P. putidaresolves enantiomeric mixtures ofcis-1,2-indandiol by further selective oxidation of the 1R, 2S-enantiomer yielding high enantiomeric purity ofcis-(1S, 2R)-indandiol, a potential intermediate in the synthesis of indinavir sulfate (CRIXIVAN), a protease inhibitor used in the treatment of AIDS. Molecular cloning ofP. putidatoluene dioxygenase inEscherichia coliconfirmed the requirement for the dihydrodiol dehydrogenase in resolving racemic mixtures ofcis-indandiol.Rhodococcussp. isolates convert indene tocis-(1S, 2R)-indandiol at high initial enantiomeric excess and one isolate also producestrans-(1R, 2R)-indandiol, suggesting the presence of monooxygenase activity. Scale up and optimization of the bioconversions to these key synthons for chiral synthesis of potential intermediates for commercial manufacture of indinavir sulfate are described.