255041-81-7

Upstream product

• 131233-30-2 (2S)-2-(1,3-dithian-2-yl)-1-propanol 
• 824-94-2 p-methoxybenzyl chloride 
• 109-80-8 1.3-propanedithiol 
• 132969-60-9 (2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropanal 

Downstream Products

• 1187567-40-3 C₃₇H₅₂O₅S₂Si 

Relevant academic research and scientific papers

Spongipyran synthetic studies. Evolution of a scalable total synthesis of (+)-spongistatin 1

Three syntheses of the architecturally complex, cytotoxic marine macrolide (+)-spongistatin 1 (1) are reported. Highlights of the first-generation synthesis include: use of a dithiane multicomponent linchpin coupling tactic for construction of the AB and CD spiroketals, and their union via a highly selective Evans boron-mediated aldol reaction en route to an ABCD aldehyde; introduction of the C(44)-C(51) side chain via a Lewis acid-mediated ring opening of a glucal epoxide with an allylstannane to assemble the EF subunit; and final fragment union via Wittig coupling of the ABCD and EF subunits to form the C(28)-C(29) olefin, followed by regioselective Yamaguchi macrolactonization and global deprotection. The second- and third-generation syntheses, designed with the goal of accessing 1 g of (+)-spongistatin 1 (1), maintain both the first-generation strategy for the ABCD aldehyde and final fragment union, while incorporating two more efficient approaches for construction of the EF Wittig salt. The latter combine the original chelation-controlled dithiane union of the E- and F-ring progenitors with application of a highly efficient cyanohydrin alkylation to append the F-ring side chain, in conjunction with two independent tactics to access the F-ring pyran. The first F-ring synthesis showcases a Petasis-Ferrier union/rearrangement protocol to access tetrahydropyrans, permitting the preparation of 750 mg of the EF Wittig salt, which in turn was converted to 80 mg of (+)-spongistatin 1, while the second F-ring strategy, incorporates an organocatalytic aldol reaction as the key construct, permitting completion of 1.009 g of totally synthetic (+)-spongistatin 1 (1). A brief analysis of the three syntheses alongside our earlier synthesis of (+)-spongistatin 2 is also presented.

Room-temperature metallation of 2-substituted 1,3-dithiane derivatives and subsequent coupling with 2,3-disubstituted oxiranes

2-Substituted 1,3-dithiane derivatives, (S)-1(t-butyldiphenylsiloxy)-2- (1,3-dithian-2-yl)propane (9), (S)-1-(t-butyldimethylsiloxy)-2-(1,3-dithian- 2-yl)propane, 1-(t-butyldiphenylsiloxy)-2-(1,3-dithian-2-yl)-2-methylpropane, and 1,2-bis-(t-butyldiphenylsiloxy)-3-(1,3-dithian-2-yl)propane, were subjected to lithiation in THF with n-BuLi at room temperature (r.t.); the resulting anions reacted with 2,3-disubstituted oxirane, trans-2-methyl-3- (triphenylmethoxymethyl)oxirane(22), at r.t., giving the coupling products in satisfactory yield. On the other hand, the lithium salt formed in ether from (S)2-(1,3-dithian-2-yl)-1-(4-methoxybenzyloxy)propane with n-BuLi at r.t. reacted with 22 at r.t. in the presence of hexamethylphosphoric triamide to afford the coupling product in moderate yield. In addition, a mixed organometallic reagent, n-BuLi/Bu2Mg, was found to be an effective metallation reagent for 9 and the resulting anion reacted with 22 to afford the coupling product in good yield.