Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters

Abstract

Bastimolide B is a polyhydroxy macrolide isolated from marine cyanobacteria displaying antimalarial activity. It features a dense array of hydroxylated stereogenic centers with 1,5-relationships along a hydrocarbon chain. These 1,5-polyols represent a particularly challenging motif for synthesis, as the remote position of the stereocenters hampers stereocontrol. Herein, we present a strategy for 1,5-polyol stereocontrolled synthesis based on iterative boronic ester homologation with enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled from readily available building blocks with full control over the remote stereocenters, enabling the total synthesis to be completed in 16 steps (LLS).

Sparteine-Free, Highly Stereoselective Construction of Complex Allylic Alcohols Using 1,2-Metallate Rearrangements

“…8 This was followed in 1995 by an extension of their 1992 observation, namely, the use of a chiral five-ring acetonide, which also provided stereocontrol with various electrophiles (Scheme 2a). 9,10 oxidation and Yamakawa chlorination. Using the methyl branch common in polyketides, only 66% ee were obtained in the preparation of the α-sulfinyl chlorides.…”

Neutral and Anionic Diboron Compounds Bearing Electron‐Precise B−B Bond

“…For example, these diborane(5) compounds can be used as neutral σ B-B diborane ligands for copper complexes (Scheme 15a). [48] Chalcogen atoms underwent oxidative insertion into the BÀ B bonds of these compounds to give new cyclized products (50 and 51), where the diborane (5) compounds 48 act as two-electron reducing agents (Scheme 15b). [49] Additionally, the reaction of arylazides with 48 generated polyheterocyclic 1,1-diboryltriazenes 52, that the nitrogen atoms of the aides can insert into the BÀ B bonds (Scheme 15c).…”

“…The cleavage of the BÀ B single bond can be utilized for the construction of BÀ E (E=O, N, C) bonds to give boryl products. [1] This approach is a very effective strategy to obtain functionalized organoboranes (such as boronic acids and their derivatives), which are essential building blocks for pharmaceutical production, [2][3][4] total synthesis, [5][6][7][8][9] and functional materials. [10][11][12][13][14] Common diborane(4) reagents, such as bis(pinacolato)diborane(4) B 2 pin 2 and bis(catecholato)diboron B 2 cat 2 (Figure 1), have been extensively used in organic synthesis to facilitate borylation reactions.…”

Site-Selective Functionalization of C(sp3) Vicinal Boronic Esters

“…This methodology was applied to the total synthesis of the 14-membered macrolactone Sch725674. Also a related approach has been used by this group to accomplish the total synthesis of the antimalarial bastimolide B, a complex macrolide isolated from marine cyanobacteria …”