Enantiomer compositions of (1R,4S)-1-butyrylamino-4-(hydroxymeth

Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing

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C07C21542

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active

06137007&

ABSTRACT:
A novel process for the preparation of (1S,4R)- or (1R,4S)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopentene-1-methanol of the formulae ##STR1## is described. This entails in the first stage (.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one of the formula ##STR2## being acylated to give a (.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one derivative of the general formula ##STR3## in which R.sup.1 denotes C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, aryl or aryloxy, the latter being reduced in the second stage to give a cyclopentene derivative of the general formula ##STR4## in which R.sup.1 has the stated meaning, the latter then being converted in the third stage biotechnologically into the (1R,4S)- or (1S,4R)-1-amino-4-(hydroxymethyl)-2-cyclopentene of the formula ##STR5## the latter being converted in the fourth stage with N-(2-amino-4,6-dichloro-5-pyrimidinyl)formamide of the formula ##STR6## into the (1S,4R)- or (1R,4S)-4-[(2-amino-6-chloro-5-formamido-4-pyrimidinyl)amino]-2-cyclopente ne-1-methanol of the formulae ##STR7## and the latter being cyclized in the fifth stage in a known manner to the final product of the formula I or II.

REFERENCES:
patent: 5371282 (1994-12-01), Nohira et al.
Luis E. Martinez et al., "Highly Efficient Enantioselective Synthesis of Carbocyclic Nucleoside Analogs Using Selective Early Transition Metal Catalysis," J. Org. Chem. 1996 vol. 61, pp. 7963-7966.
Michael T. Crimmins et al., "An Efficient Asymmetric Approach to Carbocyclic Nucleosides: Assymmetric Synthesis of 1259089, a Potent Inhibitor of HIV Reverse Transcriptase," J. Org. Chem. 1996, vol. 61, pp. 4,192-93.
Jeffrey Campbell et al., "Chirospecific Synthesis and Precursors of Cyclopentene and Cylopentene Carbocyclic Nucleosides by [3+3]-Coupling and Transannular Alkylation," J. Org. Chem. 1995, vol. 60, pp. 4602-4616.

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