Studies on the Stereo‐ and Enantioselective Synthesis of 11,12‐epoxy‐Sarcophytol‐A, 11,12‐epoxysarcophytol‐A acetate and 11,12‐epoxy‐cembrene‐C. Synthesis of 5,9,13‐trimethyl‐2‐isopropyl‐12(S),12(S)‐epoxy‐14‐bromo‐2(Z),4(E),8(E)‐tetradecatrienenitrile

Abstract

An efficient synthesis of 5,9,13-trimethy1-2-isopropyl-l2(S) , 13(S)-epoxy-l4-bromo-2(2), 4(E) ,8(El-tetradecatrienenitrile, a key intermediate in the synthesis of antitumor oembranoids including 11,12-epoxy-sarcophytol-A ,11 , 12-epoxysarcophytol-A acetate and 11 12-epoxycembrene-C, was first described through seven step sequence in -32 % overall yield from E, E-farnesol.11 , 12-Epoxysarcophytol-A 1 and 11 , 12-epoxysarcophytol-A acetate 2l, two marine cembranoids, were isolated in 1983 from the soft coral I *-.The geometrical structures of 1 and 2 have been confirmed to be 12, 3E, 7E and the absolute configurations have been determined as 14s and inferred as llS and 12s. 11, 12-Epoxycembrene-C 31*2 was also a marine cembranoid diterpene, which was isolated in 1978 from the soft coral Sinvloria qrqi and in 1983 from the soft coral Ldqh#wn . The geometrical structure of 3 has been assigned to be l E , 3E, 7E and the absolute configuration has been inferred as 11S, 12s. In view of the challenging structural features and unknown bioactivities of cembranoids 1 -3, we wish to search for a practical synthesis for them. R=OH2 R=OAc 3 R = l l Our synthetic strategy starting from E, Efarnesol 8 outlined in scheme-l involves three keysteps : ( 1 ) stereeand enantioselective synthesis of the conjugated 22, 4E-dienal 5;( 2 ) macrocyclization of 5 using modified Takahashi's protected cyanohydrin procedure', and ( 3 ) enantioselective reduction of the ketone 4 to 1. Herein we describe a full account of the synthesis of 6 (scheme 2). Scheme-1-509 -