Claims
- 1. A process for the preparation of the (3R,4S)-diol of the formula: ##STR5## wherein at each occurrence R.sub.3 is independently selected from hydrogen and an N-protecting group comprising
- (a) reaction of the (3R,4R)-diol of the formula: ##STR6## wherein R.sub.3 is R*OC(O)-- wherein R* is loweralkyl or benzyl with a compound of the formula R.sub.7 C(OR.sub.8).sub.3 wherein R.sub.7 is hydrogen, loweralkyl, phenyl or benzyl and R.sub.8 is loweralkyl to provide a compound of the formula: ##STR7## (b) reaction of the product of step a with R**SO.sub.2 Cl or (R**SO.sub.2).sub.2 O wherein R** is methyl, trifluoromethyl or 4-methylphenyl to provide the sulfonate derivative of the product of step a;
- (c) heating the product of step b in an inert solvent to provide a compound of the formula: ##STR8## (d) reaction of the product of step c with a strong base.
- 2. The process of claim 1 wherein R.sub.3 is carbonylbenzyloxy and R.sub.7 is CH.sub.3.
- 3. A process for the preparation of the (3R,4S)-diol of the formula: ##STR9## wherein at each occurrence R.sub.3 is independently selected from hydrogen and an N-protecting group comprising
- (a) reaction of the (3R,4R)-diol of the formula: ##STR10## wherein R.sub.3 is carbonylbenzyloxy with CH.sub.3 C (OCH.sub.2 CH.sub.3).sub.3 to provide a compound of the formula: ##STR11## wherein R.sub.3 is carbonylbenzyloxy and R.sub.7 is CH.sub.3 ; (b) reaction of the product of step a with methanesulfonylchloride to provide the methansulfonate-derivative of the product of step a;
- (c) heating the product of step b in an inert solvent to provide a compound of the formula: ##STR12## (d) reaction of the product of step c with a strong base.
- 4. A process for the preparation of the (3R,4S)-diol of the formula: ##STR13## wherein R.sub.3 is hydrogen comprising (a) reaction of the (3R,4R)-diol of the formula: ##STR14## wherein R.sub.3 is carbonylbenzyloxy with CH.sub.3 C (OCH.sub.2 CH.sub.3).sub.3 to provide a compound of the formula: ##STR15## wherein R.sub.3 is carbonylbenzyloxy and R.sub.7 is CH.sub.3 ; (b) reaction of the product of step a with methanesulfonylchloride to provide the methansulfonate-derivative of the product of step a;
- (c) heating the product of step b in dimethylformamide in the presence of aqueous ammonium chloride to provide a compound of the formula: ##STR16## wherein R.sub.3 is carbonylbenzyloxy and R.sub.7 is CH.sub.3 ; and (d) reaction of the product of step c with a strong base.
- 5. A process for the preparation of the (3R,4R)-diol of the formula: ##STR17## wherein R.sub.3 is hydrogen or an N-protecting group comprising (a) reaction of N-protected L-phenylalaninal with a mixture of VCI.sub.3 (THF).sub.3 and zinc dust to produce a mixture of the (3R,4R)-, (3R,4S)- and (3S,4S)-diols of the formula: ##STR18## (b) reaction of the mixture of diols from step a with acetone and sulfuric acid to produce a mixture of the acetonides resulting from the (3R,4R)-, (3R,4S)- and (3S,4S)-diols;
- (c) separation by selective crystallization of the acetonide resulting from the (3S,4S)-diol from the acetonides resulting from the (3R,4R)-diol and the (3R,4S)-diol;
- (d) reaction of the mixture of acetonides resulting from the (3R,4R)- and (3R,4S)-diols with hydrochloric acid to selectively cleave the acetonide resulting from the (3R,4R)-diol, producing a mixture of the (3R,4R)-diol and the acetonide resulting from the (3R,4S)-diol; and
- (e) separation by selective crystallization of the (3R,4R)-diol.
- 6. The process of claim 5 wherein R.sub.3 is carbonylbenzyloxy.
- 7. A process for the preparation of the (3R,4R)-diol of the formula: ##STR19## wherein R.sub.3 is hydrogen or an N-protecting group comprising (a) reaction of N-protected L-phenylalaninal with a mixture of VCI.sub.3 (THF).sub.3 and zinc dust to produce a mixture of the (3R,4R)-, (3R,4S)- and (3S,4S)-diols of the formula: ##STR20## (b) reaction of the mixture of diols from step a with acetone and sulfuric acid to produce a mixture of the acetonides resulting from the (3R,4R)-, (3R,4S)- and (3S,4S)-diols;
- (c) separation by selective crystallization of the acetonide resulting from the (3S,4S)-diol from the acetone/H.sub.2 SO.sub.4 solution of the mixture of acetonides resulting from the (3R,4R)-diol and the (3R,4S)-diol;
- (d) addition of water to the acetone/H.sub.2 SO.sub.4 solution of the mixture of acetonides of the (3R,4R)-diol and the (3R,4S)-diol resulting from step c, followed by heating; and
- (e) separation by selective crystallization of the (3R,4R)-diol.
- 8. The process of claim 7 wherein R.sub.3 is carbonylbenzyloxy.
- 9. A process for the preparation of the (3R,4R)-diol of the formula: ##STR21## where R.sub.3 is carbonylbenzyloxy comprising (a) reaction of N-carbonylbenzyloxy-L-phenylalaninal with a mixture of VCI.sub.3 (THF).sub.3 and zinc dust to produce a mixture of the (3R,4R)-, (3R,4S)- and (3S,4S)-diols of the formula: ##STR22## wherein R.sub.3 is carbonylbenzyloxy; (b) reaction of the mixture of diols from step a with acetone and sulfuric acid to produce a mixture of the acetonides resulting from the (3R,4R)-, (3R,4S)- and (3S,4S)-diols;
- (c) separation by selective crystallization of the acetonide resulting from the (3S,4S)-diol from the acetonides resulting from the (3R,4R)-diol and the (3R,4S)-diol;
- (d) reaction of the mixture of acetonides resulting from the (3R,4R)- and (3R,4S)-diols with hydrochloric acid to selectively cleave the acetonide resulting from the (3R,4R)-diol, producing a mixture of the (3R,4R)-diol and the acetonide resulting from the (3R,4S)-diol; and
- (e) separation by selective crystallization of the (3R,4R)-diol.
- 10. A process for the preparation of the (3R,4R)-diol of the formula: ##STR23## wherein R.sub.3 is carbonylbenzyloxy comprising (a) reaction of N-carbonylbenzyloxy-L-phenylalaninal with a mixture of VCI.sub.3 (THF).sub.3 and zinc dust to produce a mixture of the (3R,4R)-, (3R,4S)- and (3S,4S)-diols of the formula: ##STR24## wherein R.sub.3 is carbonylbenzyloxy; (b) reaction of the mixture of diols from step a with acetone and sulfuric acid to produce a mixture of the acetonides resulting from the (3R,4R)-, (3R,4S)- and (3S,4S)-diols;
- (c) separation by selective crystallization of the acetonide resulting from the (3S,4S)-diol from the acetone/H.sub.2 SO.sub.4 solution of the mixture of acetonides resulting from the (3R,4R)-diol and the (3R,4S)-diol;
- (d) addition of water to the acetone/H.sub.2 SO.sub.4 solution of the mixture of acetonides of the (3R,4R)-diol and the (3R,4S)-diol resulting from step c, followed by heating; and
- (e) separation by selective crystallization of the (3R,4R)-diol.
Parent Case Info
This is a continuation-in-part of U.S. patent application Ser. No. 885,575, filed May 19, 1992, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 746,020, filed Aug. 15, 1991, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 616,170, filed Nov. 20, 1990, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 518,730, filed May 9, 1990, now U.S. Pat. No. 5,142,056, which is a continuation-in-part of U.S. patent application Ser. No. 456,124, filed Dec. 22, 1989, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 405,604, filed Sep. 8, 1989, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 355,945, filed May 23, 1989, now abandoned.
Government Interests
This invention was made with Government support under contract number AI27220 awarded by the National Institute of Allergy and Infectious Diseases. The Government has certain rights in this invention.
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Continuation in Parts (7)
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Number |
Date |
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Parent |
885575 |
May 1992 |
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Parent |
746020 |
Aug 1991 |
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Parent |
616170 |
Nov 1990 |
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Parent |
518730 |
May 1990 |
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Parent |
456124 |
Dec 1989 |
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Parent |
405604 |
Sep 1989 |
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Parent |
355945 |
May 1989 |
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