149715-96-8Relevant articles and documents
Spongipyran synthetic studies. Evolution of a scalable total synthesis of (+)-spongistatin 1
Smith III, Amos B.,Sfouggatakis, Chris,Risatti, Christina A.,Sperry, Jeffrey B.,Zhu, Wenyu,Doughty, Victoria A.,Tomioka, Takashi,Gotchev, Dimitar B.,Bennett, Clay S.,Sakamoto, Satoshi,Atasoylu, Onur,Shirakami, Shohei,Bauer, David,Takeuchi, Makoto,Koyanagi, Jyunichi,Sakamoto, Yasuharu
supporting information; experimental part, p. 6489 - 6509 (2011/02/25)
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.
The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: Fragment couplings, completion of the synthesis, analogue generation and biological evaluation
Paterson, Ian,Chen, David Y.-K.,Coster, Mark J.,Acena, Jose L.,Bach, Jordi,Wallace, Debra J.
, p. 2431 - 2440 (2007/10/03)
The antimitotic marine macrolide altohyrtin A/spongistatin 1 (1) has been synthesised in a highly convergent and stereocontrolled manner, thus contributing to the replenishment of the largely exhausted material from the initial isolation work. Coupling of
Total synthesis of (+)-spongistatin 1. An effective second-generation construction of an advanced EF Wittig salt, fragment union, and final elaboration.
Smith 3rd., Amos B,Zhu, Wenyu,Shirakami, Shohei,Sfouggatakis, Chris,Doughty, Victoria A,Bennett, Clay S,Sakamoto, Yasuharu
, p. 761 - 764 (2007/10/03)
A stereocontrolled, total synthesis of (+)-spongistatin 1 (1) has been achieved. Union of a second-generation EF Wittig salt (+)-3 with the advanced ABCD aldehyde (-)-4, followed by regioselective macrolactonization and global deprotection afforded (+)-sp
