191671-39-3

Upstream product

• 73346-73-3 (4S,5S)-diethyl 2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate 
• 73346-74-4 (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol 
• 98-59-9 p-toluenesulfonyl chloride 
• 145554-06-9 [(4R,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol 

Downstream Products

• 920034-41-9 2-((2R,3S,4S,5R,6R)-6-((E)-1-(2-(((2S,4R,6R)-6-((1R,2E,4E,6R,8E)-9-bromo-1-(tert-butyldiphenylsilanyloxy)-6-methoxy-3-methylnona-2,4,8-trienyl)-2,4-dimethoxytetrahydro-2H-pyran-2-yl)methyl)oxazol-4-yl)prop-1-en-2-yl)-4-(4-methoxybenzyloxy)-3,5-dimethyltetrahydro-2H-pyran-2-yl)ethanol 
• 920034-29-3 2-(((2S,4R,6R)-6-((1R,2E,4E,6R,8E)-9-bromo-1-(tert-butyldiphenylsilanyloxy)-6-methoxy-3-methylnona-2,4,8-trienyl)-2,4-dimethoxytetrahydro-2Hpyran-2-yl)methyl)-4-((E)-2-((2R,3R,4S,5S,6R)-6-(2-(tert-butyldimethylsilanyloxy)ethyl)-4-(4-methoxybenzyloxy)-3,5-dimethyltetrahydro-2H-pyran-2-yl)prop-1-enyl)oxazole 
• 920034-28-2 (R,E)-4-((2R,4R,6S)-6-((4-((E)-2-((2R,3R,4S,5S,6R)-6-(2-(tert-butyldimethylsilanyloxy)ethyl)-4-(4-methoxybenzyloxy)-3,5-dimethyltetrahydro-2Hpyran-2-yl)prop-1-enyl)oxazol-2-yl)methyl)-4,6-dimethoxytetrahydro-2H-pyran-2-yl)-4-(tert-butyldiphenylsilanyloxy)-2-methylbut-2-enal 
• 920034-40-8 (R,E)-4-(tert-butyldiphenylsilanyloxy)-4-((2R,4R,6S)-6-((4-((E)-2-((2R,3R,4S,5S,6R)-6-(2-hydroxyethyl)-4-(4-methoxybenzyloxy)-3,5-dimethyltetrahydro-2H-pyran-2-yl)prop-1-enyl)oxazol-2-yl)methyl)-4,6-dimethoxytetrahydro-2H-pyran-2-yl)-2-methylbut-2-enal 
• 920034-39-5 (2S,4R,6R)-6-((R,E)-1-(tert-butyldiphenylsilanyloxy)-4-hydroxy-3-methylbut-2-enyl)-2-((4-((E)-2-((2R,3R,4S,5S,6R)-6-(2-hydroxyethyl)-4-(4-methoxybenzyloxy)-3,5-dimethyltetrahydro-2H-pyran-2-yl)prop-1-enyl)oxazol-2-yl)methyl)-4-methoxytetrahydro-2H-pyran-2-ol 
• 920034-27-1 (2S,4R,6R)-2-((4-((E)-2-((2R,3R,4S,5S,6R)-6-(2-(tert-butyldimethylsilanyloxy)ethyl)-4-(4-methoxybenzyloxy)-3,5-dimethyltetrahydro-2H-pyran-2-yl)prop-1-enyl)oxazol-2-yl)methyl)-6-((R,E)-2,2,7,10,10,11,11-heptamethyl-3,3-diphenyl-4,9-dioxa-3,10-disiladodec-6-en-5-yl)-4-methoxytetrahydro-2H-pyran-2-ol 
• 920034-36-2 (R,E)-5-((2R,4R)-4-methoxy-6-(phenylthio)-tetrahydro-2H-pyran-2-yl)-2,2,7,10,10,11,11-heptamethyl-3,3-diphenyl-4,9-dioxa-3,10-disiladodec-6-ene 
• 920034-25-9 (4R,6R)-6-((R,E)-2,2,7,10,10,11,11-heptamethyl-3,3-diphenyl-4,9-dioxa-3,10-disiladodec-6-en-5-yl)-4-methoxy-tetrahydropyran-2-one 
• 920018-80-0 (3R,4E,6E,8R)-8-(tert-butyldiphenylsilanyloxy)-3-methoxy-8-((4R)-4-methoxy-6-oxotetrahydro-2H-pyran-2-yl)-6-methylocta-4,6-dienal 
• 920018-67-3 (4R,6R)-6-((1R,2E,4E,6R)-1-(tert-butyldiphenylsilyloxy)-6-methoxy-3-methylnona-2,4,8-trienyl)-4-methoxy-tetrahydro-2H-pyran-2-one 
• 920018-66-2 tert-butyl-(1R,2E,4E,6R)-6-methoxy-1-(((2R,4R,6R)-4-methoxy-6-(phenylthio)-tetrahydro-2H-pyran-2-yl)-3-methylnona-2,4,8-trienyloxy)diphenylsilane 
• 920018-60-6 (R)-2-(tert-butyldiphenylsilanyloxy)-2-((2R,4R,6S)-4-methoxy-6-(phenylthio)tetrahydro-2H-pyran-2-yl)ethanol 
• 1407517-56-9 (R)-2-(tert-butyldiphenylsilanyloxy)-2-((2R,4R,6R)-4-methoxy-6-(phenylthio)tetrahydro-2H-pyran-2-yl)ethanol 
• 1407517-37-6 ((1R,2E,4E,6R,8E)-9-bromo-1-((2R,4R,6R)-4,6-dimethoxytetrahydro-2H-pyran-2-yl)-6-methoxy-3-methylnona-2,4,8-trienyloxy)(tertbutyl)diphenylsilane 

Relevant academic research and scientific papers

Total synthesis of phorboxazole A. 1. Preparation of four subunits

(Chemical Equation Presented) Four subunits of the potent antitumor agent phorboxazole A were constructed; fragments C20-C32 and C9-C19 containing tetrahydropyrans A and B, respectively, were assembled using palladium-catalyzed intramolecular alkoxycarbonylation.

Total synthesis of the marine toxin phorboxazole A using palladium(ii)-mediated intramolecular alkoxycarbonylation for tetrahydropyran synthesis

The potent antitumor agent phorboxazole A was synthesized from six subunits comprising C1-C2 (115), C3-C8 (98), C9-C19 (74), C20-C32 (52), C33-C41 (84) and C42-C46 (85). Tetrahydropyrans B and C containing cis-2,6-disubstitution were fabricated via palladium(ii)-mediated intramolecular alkoxycarbonylation which, in the case of tetrahydropyran C, was carried out with catalytic palladium(ii) and p-benzoquinone as the stoichiometric re-oxidant. Tetrahydropyran D was obtained by a stereoselective tin(iv)-catalyzed coupling of a C9 aldehyde with an allylsilane, and the C19-C20 connection was made using a completely stereoselective Wittig-Schlosser (E) olefination. Coupling of the oxazole C32 methyl substituent with the intact C33-C46 δ-lactone 3 was accompanied by elimination of the vinyl bromide to a terminal alkyne, but the C32-C33 linkage was implemented successfully with 83 and C33-C41 lactone 84. The C42-C46 segment of the side chain was then appended via Julia-Kocienski olefination. The macrolide portion of phorboxazole A was completed by means of an Ando-Still-Gennari intramolecular (Z)-selective olefination at C2-C3 which required placement of a (dimethoxyphosphinyl)acetate moiety at C24. Final deprotection led to phorboxazole A via a route in which the longest linear sequence is 37 steps and the overall yield is 0.36%.