xv ABSTRACT STUDY ON THE TOTAL SYNTHESIS OF

ABSTRACT
STUDY ON THE TOTAL SYNTHESIS OF OMAEZALLENE
DERIVATIVE
(SYNTHESIS OF 7TH INTERMEDIATE COMPOUND)
Nurcahyo Iman Prakoso
12/336354/PPA/03762
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 1,3diol 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.
Keywords : omaezallene derivative, 5-Bromo-5-[3-(tert-butyl-dimethylsilanyloxy)-tetrahydro-furan-2-yl]-4-trimethylsilanyloxy-pent-2-en-1-ol
xv
INTISARI
STUDI TOTAL SINTESIS SENYAWA TURUNAN OMAEZALLENE
(SINTESIS SENYAWA INTERMEDIET KE-7)
Nurcahyo Iman Prakoso
12/336354/PPA/03762
Sintesis senyawa intermediet ke-7, (5-Bromo-5-[3-(tert-butyl-dimethylsilanyloxy)-tetrahydro-furan-2-yl]-4-trimethylsilanyloxy-pent-2-en-1-ol) 55a dan
55b dari senyawa turunan omaezallene tanpa gugus bromodiene telah berhasil
dilakukan. Sintesis dari kedua senyawa enantioner, 55a dan 55b dilakukan
melalui 15 tahap reaksi dan dapat dibagi menjadi 4 kelompok besar reaksi dengan
3 senyawa intermediet penting. Senyawa-senyawa tersebut adalah 1,3-diol
terproteksi 44, alkohol tak jenuh 48, dan bromotetrahidrofuran alkohol 50.
Senyawa 1,3-diol terproteksi 44 disintesis melalui 4 tahap reaksi dan
menghasilkan yield sebesar 95%. Reaksi proteksi secara parsial cis-2-butena-1,4diol melalui reaksi proteksi PMB memberikan alkohol 41 dengan yield 46%.
Reaksi epoksidasi asimetris Sharpless alkohol 41 memberikan epoksida alkohol
42 dengan yield 42%. Pembukaan cincin epoksida dengan Red-Al menghasilkan
1,3-diol 43 dengan yield 99%. Reaksi proteksi dengan TBS menghasilkan 1,3-diol
terproteksi 44. Alkohol tak jenuh 48 disintesis melalui 4 tahap reaksi dan
menghasilkan yield sebesar 47%. Deproteksi PMB melalui reaksi dengan DDQ,
diikuti oksidasi TEMPO dan E-selektif Wittig secara in situ menghasilkan ester
tak jenuh 47 dengan yield 52%. Reduksi ester tak jenuh 47 menggunakan DIBAL
menghasilkan alkohol tak jenuh 48. Bromotetrahidrofuran alkohol 50 disintesis
melalui 2 tahap reaksi dan menghasilkan yield sebesar 13%. Deproteksi parsial
gugus TBS menggunakan HF-Piridine dan diikuti dengan reaksi
bromosikloeterifikasi
menggunakan
NBS-asetonitril
menghasilkan
bromotetrahidrofuran alkohol 50. Alkohol tak jenuh 55a dan 55b dengan yield
21% dan 12% disintesis melalui 5 tahap reaksi. Oksidasi melalui DMP, diikuti
adisi asimetris dengan TMS-CN, reduksi selektif DIBAL untuk menghasilkan
aldehida, reaksi Horner-Wadsworth-Emmons dan diakhiri dengan reaksi reduksi
DIBAL menghasilkan alkohol tak jenuh 55a dan 55b. Nilai konfigurasi absolut
dari produk tersebut juga sudah ditentukan pada setiap langkah sintesis.
Kata kunci : turunan omaezallene, 5-Bromo-5-[3-(tert-butil-dimetil-silaniloksi)tetrahidrofuran-2-il]-4-trimetilsilaniloksi-pent-2-en-1-ol
xvi