53 プナグランジンおよび関連体の合成

概要

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Antineoplastic punaglandins and related compounds have been synthesized. Condensation of (S)-3-chloro-4-t-butyldimethylsiloxy-2-cyclopentenone and the lithium derivative generated from 3-tributylstannyl-1,2-octadiene with n-butyllithium at -78℃ gives after desilylation (3R,5S)-1-chloro-3,5-dihydroxy- 3-(2-octyn-1-yl)-cyclopentene. High diastereoselectivity, giving the cis diol, is secured in this propargylation reaction. Partial hydrogenation of the triple bond using Lindlar catalyst followed by oxidation of the secondary hydroxy group with pyridinium dichromate gives (4R)-2-chloro-4-hydroxy-4-((Z)-2-octen-1-yl)-2-cyclopentenone. The punaglandin whole skeleton is constructed by aldol condensation of the lithium enolate of the cyclopentenone and (2R,3S)-6-carbomethoxy-2,3-diacetoxyhexanal at -78℃. Aldol dehydration and removal of the silyl protective group lead to a mixture of punaglandin 4 and its Z-isomer (structures postulated by Scheuer). (±)-5,6-Bisdeacetoxy-14, 15; 17, 18-tetrahydropunaglandin, a structurally simpler punaglandin analogue, shows the antineoplastic activity for L1210 tumor cells comparable to punaglandins.
天然有機化合物討論会の論文
1985-09-07