Synthetic process for the preparation of taxol and other tricyclic and tetracyclic taxanes
AssigneeFlorida State University
InventorsRobert A. Holton, Carmen Somoza, Hyeong B. Kim, Mitsuru Shindo, Ronald J. Biediger, P. Douglas Boatman, Chase Smith, Feng Liang, Krishna Murthi
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Abstract
Process for the synthesis of taxol and other tricyclic and tetracyclic taxanes.
Claims7
A process for the preparation of an intermediate useful in the synthesis of taxol or another tricyclic or tetracyclic taxane comprising reacting a compound having the formula:
- ##STR35## with lithium tetramethylpiperidide to form a compound having the formula:
- ##STR36## wherein P.sub.10 and P.sub.13 are hydroxy protecting groups.
A process for the preparation of an intermediate useful in the synthesis of taxol or another tricyclic or tetracyclic taxane comprising reacting a compound having the formula:
- ##STR37## with lithium tetramethylpiperidide and camphosulfonyl oxaziridine to form a compound having the formula:
- ##STR38## wherein P.sub.10 and P.sub.13 are hydroxy protecting groups.
A process for the preparation of an intermediate useful in the synthesis of taxol or another tricyclic or tetracyclic taxane comprising reacting a compound having the formula:
- ##STR39## with lithium diisopropylamide to form a compound having the formula:
- ##STR40## wherein P.sub.10 and P.sub.13 are hydroxy protecting groups and R is lower alkyl.
A process for the preparation of an intermediate useful in the synthesis of taxol or another tricyclic or tetracyclic taxane comprising reacting a compound having the formula:
- ##STR41## with diazabicycloundecane to form a compound having the formula:
- ##STR42## wherein P.sub.13 is a hydroxy protecting group;
- R.sub.7a is hydrogen, halogen, or --OR.sub.28 ;
- R.sub.10a is hydrogen, --OCOR.sub.29, hydroxy, or protected hydroxy;
- R.sub.28 is hydrogen, acyl, or hydroxy protecting group;
- and
- R.sub.29 is hydrogen, alkyl, alkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl;
- T.sub.4b and T.sub.4a are hydroxy;
- T.sub.5 is --OMs or --OTs;
- and
- Ms is CH.sub.3 SO.sub.2 -- and Ts is toluenesulfonyl.
A process for the preparation of an intermediate useful in the synthesis of taxol or another tricyclic or tetracyclic taxane comprising reacting a compound having the formula:
- ##STR43## with KOtBu and (PhSeO).sub.2 O to form a compound having the formula:
- ##STR44## wherein P.sub.13 is a hydroxy protecting group;
- R.sub.2 is hydrogen, hydroxy, or --OCOR.sub.31 ;
- R.sub.4a is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyano, hydroxy, or --OCOR.sub.30 ;
- R.sub.7a is hydrogen, halogen, or --OR.sub.28 ;
- R.sub.28 is hydrogen, acyl, or hydroxy protecting group;
- and
- R.sub.30 and R.sub.31 are independently hydrogen, alkyl, alkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl.
Dependencies are inferred from the claim text.