Synthesis of metabolites of S-1452, an orally active thromboxane A2 receptor antagonist.
The synthesis of 16 metabolites of S-1452, an orally active thromboxane A2 (TXA2) receptor antagonist, is described. Regioselective hydroxylation at C-5 or C-6 of the bicyclo[2.2.1]heptane skeleton of the optically active intermediate 16 was attempted by using 9-borabicyclo[3.3.1]nonane followed by H2O2 or m-chloroperbenzoic acid (m-CPBA) and then LiA1H4, to obtain the hydroxylated product 17a or 17b, respectively. Modification of the C-2 substituent of 17a and 17b afforded eight metabolites of S-1452. Eight non-hydroxylated metabolites were synthesized by using a similar reaction sequence.
Watanabe
F
F
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Matsuura
T
T
Shirahase
K
K
Ohtani
M
M
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C056566:S 145