Total Synthesis of (+)-Calyculin A and (−)-Calyculin B:  Asymmetric Synthesis of the C(9−25) Spiroketal Dipropionate Subunit

Abstract

An asymmetric synthesis of the stereochemically fully endowed C(9−25) spiroketal fragment (+)-BC of the calyculins (1−8) is described. Highlights of the synthesis include: a highly diastereoselective IBr-induced iodocarbonate cyclization to introduce the C(21) stereocenter in epoxide (+)-18, fragment unions exploiting the reaction of acyl anion equivalents with epoxides to construct masked advanced aldols (−)-35 and (+)-71 as single diastereomers, chelation-controlled addition of the C(14−15) vinyl group to aldehyde (+)-38 to set the stereogenicity at C(16), selective reduction of the C(13) ketone via 1,3-induction, and development of an orthogonal protection scheme permitting both convenient installation of the C(17) phosphate group and flexibility in subsequent fragment couplings.

Modular Total Synthesis of Rhizopodin: A Highly Potent G‐Actin Dimerizing Macrolide

“…According to the report by Smith et al., two conformations of compound 19 might, in principle, be involved. Presumably owing to the Thorpe–Ingold effect, compound 19 is expected to reside in either an axial or an equatorial arrangement with respect to the proton of the dithiane, as shown in Figure 6 68. A second DFT study revealed that, unsurprisingly, structure 19‐ax (left) was energetically favored, although it would only allow slow axial deprotonation.…”

“…For a related system, Smith and co‐workers extensively studied several sterically encumbered dithianes, which they were able to metalate without problem 68. However, a related substrate to compound 19 , which contained an allyl‐ether functionality, could not be deprotonated either.…”

Total Synthesis and Stereochemical Reassignment of Mandelalide A

“…The synthesis of fragment 5 commenced from the known homoallylic alcohol 11 7. As shown in Scheme , homoallylic alcohol 11 was protected as its 2,6‐dichlorobenzyl ether, and the terminal alkene was subjected to hydroboration with 9‐BBN to afford the corresponding primary alcohol 12 in 90 % yield.…”

Functionalized organolithium compounds in total synthesis

“…14 A similar enantioselective methodology starting also from an O-alkylated Scheme 2. allyl alcohol has been used for the preparation of the marine sponge metabolites (C)-caliculin A and (K)-caliculin B. 15 In another example of the use of a lithium-boron-exchange, 1,3-dioxene was deprotonated with sec-butyllithium to generate organolithium 15 which reacted with a-chloroallyl boronate 16 to give compound 17 which has been employed in the addition to an aldehyde for the creation of the conjugated polyenic system in a synthesis of phenalamide A 2 (18), a natural product isolated from gliding bacteria (Scheme 4). 16 An example of the use of an a-oxygenated organolithium prepared from a heterocyclic allyl system is shown in the addition of 5-lithio-4-methoxy-3-methyl-2(5H)-furanone (20), obtained by deprotonation with n-butyllithium of the corresponding 2(5H)-furanone, to aldehyde 19, the resulting alcohols 21 being intermediates in the total synthesis of the Stemona alkaloids (G)-didehydrostemofoline (asparagamine A) (22) and (G)-isodidehydrostemofoline (23) (Scheme 5).…”