Synthesis of the Oxygenated Pactamycin Core

Abstract

[structure: see text]. Pactamycin, one of the most complex and densely functionalized aminocyclitol antibiotics known, presents synthetic challenges that include reactivity and sterics, relative and absolute stereochemistry, and functional group compatibility and protection. An approach is reported that features four different types of (cyclopentane) face selective functionalization reactions and results in a polyfunctionalized and appropriately protected intermediate that incorporates all the core carbons and the oxygenated functionality of the target.

Diastereocontrolled Construction of Pactamycin’s Complex Ureido Triol Functional Array

“…The molecule is heteroatom-rich and contains urea, salicylate, and aniline functionality about the densely-substituted core. The synthetic challenge posed by this complex target had only received limited attention in the literature with two synthetic studies, 6 until the first total synthesis was realized in 2011 by Hanessian and coworkers. 7 This Letter details progress on a pactamycin core synthesis, specifically highlighting issues associated with the diastereoselective construction of the C5 tertiary carbinol.…”

Asymmetric Synthesis of the Aminocyclitol Pactamycin, A Universal Translocation Inhibitor

“…Hanessian and coworkers reported the landmark total synthesis in 2011, 9,10 and Isobe, Knapp, Looper, Nishikawa, and our group have disclosed access to advanced core intermediates by varying methods. [11][12][13][14][15] An inspection of these approaches reveals two common challenges one faces in assembling the core structure: i) execution of chemo-and stereoselective reactions in a highly congested chemical environment and ii) the method by which the unusual functionality of 1 is introduced. The Hanessian group observed of numerous side reactions due to functional group propinquity.…”

Control of the Regio‐ and Diastereoselectivity for the Preparation of Highly Functionalized Terpenic Cyclopentanes through Radical Cyclization

“…The stereocontrolled synthesis of highly versatile cyclopentane fragments to generate advanced intermediates for the synthesis of biologically active natural products has been achieved in recent years with jatrophane diterpenes, [8] pactamycin, [9] kansuinine, [10] and viridenomycin. [11] The preparation, in moderate yields, of five-membered carbocycles from 2,3-epoxy alcohols by using Ti III for the oxirane opening has also been reported.…”