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Synthesis of 2‐Oxacortexone and its Effect on Ca 2+ Uptake in Bovine Spermatozoa
Author(s) -
Frimer Aryeh A.,
Aljadeff Gladis,
Rubinstein Sara,
Breitart Haim
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300502
Subject(s) - chemistry , lactol , enol , lactone , ethylene , saponification , autoxidation , ring (chemistry) , oxygen atom , steroid , stereochemistry , diene , medicinal chemistry , organic chemistry , molecule , catalysis , biochemistry , natural rubber , hormone
Low temperature base catalyzed autoxidation (BCA) of the A‐ring of 21‐acetoxypregn‐5‐ene‐3,20‐dione 20‐ethylene ketal ( 7 ) resulted in the saponification of the ester with the concomitant formation of 2,21‐dihydroxypregna‐1,4‐diene‐3,20‐dione 20‐ethylene ketal ( 8 ) Continued BCA at ambient temperature, converts the latter to 1,21‐dihydroxy‐2‐oxaprogesterone 20‐ethylene ketal ( 9 ), which is reduced by NaBH 4 to the 2‐oxasteroid, 21‐hydroxy‐2‐oxaprogesterone 20‐ethylene ketal ( 10 ). Treatment of enol 8 , lactol 9 , 9 , and lactone 10 with aqueous acid generates the corresponding deprotected analogs 2,21‐dihydroxypregna‐1,4‐diene‐3,20‐dione (enol 11 ), 1,21‐dihydroxy‐2‐oxaprogesterone (lactol 12 ), and 2‐oxacortexone ( 2 ‐oxadesoxycorticosterone, 21‐hydroxy‐2‐oxaprogesterone, lactone 13 ). In bovine spermatozoa, neither 2‐oxasteroid ketal 10 nor its deprotected analog 13 stimulated Ca 2+ uptake. In high concentration (0.5 mM), the inhibition of Ca 2+ uptake is only 37% for 13 , as compared to 83% found with the parent steroid, cortexone (desoxycorticosterone, 21‐hydroxyprogesterone, 5 ). The difference in molecular structure between 13 and 5 indicates the importance of the oxygen atom in ring A in achieving the protective effect of the steroid. Ketalization of the C‐20 carbonyl is not important for protection. Thus it seems that by replacing C‐2 by an oxygen atom we can reduce the biological damage caused by relatively high concentrations of steroid treatment. These results are highly significant when treatment of patients with high doses of steroids is considered.