Asymmetric Total Syntheses of Aetheramides and Their Stereoisomers: Stereochemical Assignment of Aetheramides

Abstract

The concise total syntheses of the potent HIV inhibitors aetheramides A and B (IC50 values of 15 and 18 nM), as well as three pairs of their stereoisomers, were achieved, which allowed the complete stereochemical assignment of aetheramides for the first time. With a longest linear sequence of 15 steps, the convergent, fully stereocontrolled route provided aetheramides A and B in 5.3% and 3.6% yields, respectively. The synthetic strategy features efficient Stille coupling for macrocyclization, asymmetric aldol reactions to establish the ambiguous stereochemistries at C-17 and C-26, and implementation of mild conditions to avoid the epimerization of the sensitive polyketide moiety and the migration of the labile lactone.

Selective Synthesis of Benzo[a]Carbazoles and Indolo[2,1‐a]‐Isoquinolines via Rh(III)‐Catalyzed C−H Functionalizations of 2‐Arylindoles with Sulfoxonium Ylides

“…Notably, the structure of 3 m was confirmed by its single crystal X‐ray diffraction analysis . This is in consistence with what has been observed by Li et al in a Rh(III)‐catalyzed synthesis of indoles from the reactions of imidamides with diazo ketoesters via C−H activation and C−C/C−N bond cleavage . As a further aspect, in addition to 2‐phenylindoles, 2‐(naphthalene‐1‐yl)indole was also suitable for this reaction to give 3 p in 52% yield.…”

Transformation of Organostannanes Based on Photocleavage of C-Sn Bond via Single Electron Transfer Process

“…C-Sn bond is known as a kind of very important carbon-metal bond, which has numerous applications in organic chemistry 1 , 2 , biological chemistry 3 – 5 , and medicinal chemistry 6 , 7 . There are three main routes for the transformation of organostannanes, including transmetalation process 8 – 10 , carbanion process 11 , and radical process 12 , 13 .…”

Enantioselective Synthesis of the C23–C33 Fragment of Aetheramide A and Its C32 Epimer

“…In the same year, a preparation of a polyketide precursor of aetheramides from a chiral furyl carbinol was reported by Revu and Prasad . The enantioselective total synthesis of aetheramides A and B and other stereoisomers thereof was accomplished by He et al from an achiral starting material in 15 steps and 5.3 % overall yield for aetheramide A and 3.6 % for aetheramide B . Still, in 2016 He et al reported the preparation of aetheramides A and B by using a different strategy (15 steps, 4.7 % overall yield) .…”

“…[5] The enantioselective total synthesis of aetheramides A and B and other stereoisomers thereof was accomplished by He et al from an achiral starting material in 15 steps and 5.3 % overall yield for aetheramide A and 3.6 % for aetheramide B. [6] Still, in 2016 He et al reported the preparation of aetheramides A and B by using a different strategy (15 steps, 4.7 % overall yield). [7] Three different approaches were also tested in the synthesis of the protected aetheramide by Revu and Prasad in 2017.…”

“…Building block 2 was to be formed by diastereoselect-ive ethynylation of (R)-mandelic aldehyde prepared from (R)mandelic acid (4). The second chiral building block 3 was expected to be prepared by a cross-metathesis reaction of methyl acrylate and the product of the enantioselective catalytic allylation of (E)-3-iodomethacryldehyde (5), which could be prepared from methyl dimethylmalonate (6). [11]…”