Convergent Synthesis of the Dihydropyran Core Containing the C1–C15 Subunit of Sorangicin A Employing Gold(I)-Catalyzed Cyclization of an Allenic Alcohol

Abstract

A convergent route to the C1-C15 subunit of sorangicin A is disclosed. The key steps include carbon-carbon bond formation using an α-chloro sulfide, regioselective hydrozirconation of an internal alkyne for the preparation of a trisubstituted iodoalkene, allene formation using the Myers-Movassaghi protocol, stereoselective reduction of allylic and propargylic ketones using Noyori's catalyst, and gold(I)-catalyzed cyclization of a β-hydroxy allene to construct the dihydropyran ring.

Stereoselective Synthesis of the C1–C22 Carbon Framework of (−)-Amphidinolide K

“…Reaction of aldehyde 49 , shown in Scheme , with mesylate 6 following Marshall’s protocol afforded alkyne 51 . Deoxygenation of the mesylate 53 using LAH afforded alkyne 55 which on hydrozirconation followed by iodine quench yielded iodo alkene 4 . An identical sequence of reactions afforded iodo alkene 57 starting from aldehyde 50 .…”

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…Dihydropyran and tetrahydropyran fragments found in natural products have been accessed from oxycyclization of β-allenols through diverse strategies. The dihydropyran C1–C15 subunit 689 of Sorangicin A, a potent antibiotic isolated from Sorangium Cellulosumi bacteria, has been synthesized through the gold-catalyzed 6-endo-trig cyclization of enantioenriched β-allenol 692a , prepared from oxidation and further asymmetric reduction of the diastereomeric mixture 692 a /692b (Scheme , reaction a) …”

“…The dihydropyran C1−C15 subunit 689 of Sorangicin A, a potent antibiotic isolated from Sorangium Cellulosumi bacteria, has been synthesized through the gold-catalyzed 6-endo-trig cyclization of enantioenriched βallenol 692a, prepared from oxidation and further asymmetric reduction of the diastereomeric mixture 692a/692b (Scheme 113, reaction a). 389 Prins-type cyclization of β-allenol 695 with dimethyl acetals 696 and 697 followed by Tsuji reduction led to the C14−C35 fragment of Eribulin (693) and the C14−C38 fragment of Halichondrin (694), respectively, two macrolides of marine origin exhibiting potent antitumor activity. Chirality transfer from enantioenriched allenols and acetals led to the stereocontrolled generation of the C27 sterocenter, and further Tsuji reduction under palladium conditions provided the stereodefined C25 center in both fragments 693 and 694 (Scheme 113, reaction b).…”

Recent Developments and Synthetic Applications of Nucleophilic Zirconocene Complexes from Schwartz's Reagent

“…In 2016, Raghafan and Nyalata also employed this kind of transformation in the preparation of a dihydropyran scaffold of the antibacterial natural product Sorangicin A (Scheme ) . The desired iodovinyl intermediate ( 145 ) was achieved in 80 % yield after the hydrozirconation/iodination sequence.…”