STUDY ON THE TOTAL SYNTHESIS OF OMAEZALLENE DERIVATIVE (SYNTHESIS OF 7th INTERMEDIATE COMPOUND)

• Main Authors: , Nurcahyo Iman P, , Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.
• Format: Theses and Dissertations NonPeerReviewed
• Published: [Yogyakarta] : Universitas Gadjah Mada 2014
• Subjects: ETD
• Online Access: https://repository.ugm.ac.id/133779/; http://etd.ugm.ac.id/index.php?mod=penelitian_detail&sub=PenelitianDetail&act=view&typ=html&buku_id=74597
• Institution: Universitas Gadjah Mada

Synthesis of 7th intermediate compound (5-Bromo-5-[3-(tert-butyldimethyl- silanyloxy)-tetrahydro-furan-2-yl]-4-trimethylsilanyloxy-pent-2-en-1-ol) 55a and 55b from omaezallene derivative without bromodiene group has been conducted. Total syntheses of both enantiomers of 55a and 55b were achieved in 15 steps and can be divided into 4 major groups of reaction with 3 important intermediate compounds. These are protected 1,3-diol 44, unsaturated alcohol 48, and bromotetrahydrofuran alcohol 50. The 95% yield of protected 1,3-diol 44 was synthesized by 4 steps of reaction. Partial protection reaction of cis-2-butene-1,4-diol via PMB protection gave protected alcohol 41 in 46% yield. Sharpless epoxidation reaction of protected alcohol 41 gave epoxide alcohol 42 in 42% yield. Open epoxide ring by Red-Al reduction produced 1,3-diol 43 in 99% yield. The TBS protection of 1,3- diol 43 yielded protected 1,3-diol 44. The 47% yield of unsaturated alcohol 48 was produced by 4 steps of reaction. Deprotection of PMB group via DDQ, TEMPO oxidation and E-selective Wittig addition by in situ reaction gave unsaturated ester 47 in 52% yield. Reduction of unsaturated ester 47 via DIBAL yielded unsaturated alcohol 48. The 13% yield of bromotetrahydrofuran alcohol 50 was produced by 2 steps of reaction. Partial deprotection of TBS group via HFPyridine and followed with bromocycloetherification via NBS-acetonitrile yielded bromotetrahydrofuran alcohol 50. The 21% yield of unsaturated alcohol 55a and 12% yield of unsaturated alcohol 55b were produced by 5 steps of reaction. There are oxidation of bromotetrahydrofuran alcohol 50 via DMP followed by asymmetric addition with TMS-CN, selective DIBAL reduction to aldehyde, Horner�Wadsworth�Emmons reaction and DIBAL reduction to unsaturated alcohol 55a and unsaturated alcohol 55b. Absolute configurations of the product were established through total synthesis.