Diversity‐oriented synthesis of diol‐based peptidomimetics as potential HIV protease inhibitors and antitumor agents

Peptidomimetic HIV protease inhibitors are an important class of drugs used in the treatment of AIDS. The synthesis of a new type of diol-based peptidomimetics is described. Our route is flexible, uses d-glucal as an inexpensive starting material, and makes minimal use of protection/deprotection cycles. Binding affinities from molecular docking simulations suggest that these compounds are potential inhibitors of HIV protease. Moreover, the antiproliferative activities of compounds 33 a, 35 a, and 35 b on HT-29, M21, and MCF7 cancer cell lines are in the low micromolar range. The results provide a platform that could facilitate the development of medically relevant asymmetrical diol-based peptidomimetic

Total Synthesis of Sinenside A

The first total synthesis of norlignan glucoside sinenside A has been accomplished. An intramolecular acetalization reaction has been employed as the key skeletal construct to forge the central cyclic disaccharide core. The trans-1,2-diol configuration present in the cyclic disaccharide of this natural product is unique and has been addressed by setting this configuration at the beginning. A 1,2-orthoester group has been selected as a handle for both sp glycosidation and for differentiation of the C2′-OH (that participates in the key acetalization reaction) of the sugar unit

Total synthesis of mangiferaelactone

Herein we document the first total synthesis of mangiferaelactone and thus establish its absolute configuration. The central nonenolide ring was constructed using ring closing metathesis and Yamaguchi esterification. The key alcohol fragment was synthesized by the Bernet–Vasella fragmentation of C-ribofuranoside

Total Synthesis of Sinenside A

The first total synthesis of norlignan glucoside sinenside A has been accomplished. An intramolecular acetalization reaction has been employed as the key skeletal construct to forge the central cyclic disaccharide core. The <i>trans</i>-1,2-diol configuration present in the cyclic disaccharide of this natural product is unique and has been addressed by setting this configuration at the beginning. A 1,2-orthoester group has been selected as a handle for both sp glycosidation and for differentiation of the C2′-OH (that participates in the key acetalization reaction) of the sugar unit

The total synthesis and structural revision of stagonolide D

The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant −OTBS deprotection and displacement of an −OMs placed next to it, resulting in the formation of the epoxide ring

Studies toward the total synthesis of Cytospolide E

In this manuscript, we describe various approaches that we have examined towards the total synthesis of Cytospolide E. We initially attempted the RCM approach employing first and second generation Grubbs and Grubbs–Hoyeda catalysts resulting in the exclusive synthesis of the Z-isomer of Cytospolide E. With the Fürstner catalyst, the dimerization involving the less hindered olefin was the exclusive event. Alternative approach documented is a successful cross-metathesis leading to a seco-acid with the requisite E-configuration and undesired macrodiolide formation during the attempted Shiina's lactonization

The Total Synthesis and Structural Revision of Stagonolide D

The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant −OTBS deprotection and displacement of an −OMs placed next to it, resulting in the formation of the epoxide ring

The Total Synthesis and Structural Revision of Stagonolide D

The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant −OTBS deprotection and displacement of an −OMs placed next to it, resulting in the formation of the epoxide ring