Estudos visando a síntese da Ieodomicina D empregando acoplamento stille

Abstract

In this work we describe studies that aim at the asymmetric convergent synthesis of linear acid Ieodomycin D, one of the four molecules isolated from the marine microorganism Bacillus sp, though the preparation of two fragments and consequent Stille coupling reaction. The first synthesized C1-C4 fragment involved the preparation of (E)-3-iodoacrylic acid from alcohol prop-2-yn-1-ol involving two steps and 37% overall yield, followed by esterification thereof to form (E)-methyl 3-iodoacrylate. The next step was the choice of the most reproducible methodology for the protection of the primary and secondary hydroxyl of the racemic diol (±)-pentane-1,4-diol. After numerous attempts at primary selective protection of the primary hydroxyl do not work, the most efficient and reproducible route was the primary selective protection of the OH functional group with the trityl group, forming the monotrityl alcohol (R)-5-(trityloxy)pentan-2-ol in 65% yield. For three more steps, the tosylated (±)-4-((tert-butyldiphenylsilyl)oxy)pentyl-4-methylbenzenesulfonate was obtained. Optimizing the best condition for the protecting groups, the next step was the synthesis of the chiral pool (-)-(R)-pentane-1,4-diol stannane from the natural L-glutamic acid in 4 steps and 39% overall yield. After the conditions for the protecting group were optimized, the chiral tosylated silyl TBDPS-OTs, from the diol (-)-pentane-1,4-diol in 4 steps. Compound (+)-(R)-tert-butyldiphenyl((5-(trityloxy)pentan-2-yl)oxy)silane was homologated via Sn2, from 5 to 7 carbons, to synthesized (+)-(R)-tert-butyl(hept-6-yn-2-yloxy)diphenylsilane chiral alkyne. With this compound in hand, a Stille coupling reaction was made with the preparation of the in situ and (R, E) -tert-butyldiphenyl ((7- (tributylstannyl)-hept-6-en-2-yl)oxy)silane resulting coupling with the (E)-methyl-3-iodoacrylate via microwaves where no formation of the coupling product was observed. Then, the use of the standard Stille reaction was employed by coupling the stannane and the alkyne, which formed a mixture that it was not possible to isolate the (R, 2E, 4E) -methyl-9 - ((tert-butyldiphenylsilyl) oxo) deca-2,4-dienoate in pure form, but its formation was observed by 13C NMR spectrum analysis. In order to optimize the synthesis of the stannane of interest and to isolate it for better spectral identification, methodologies were tested, but without success, and it was not possible to conclude the total synthesis of Ieodomycin D.