The first and asymmetric total synthesis of cyclocitrinol, an unusual C25 steroid, has been accomplished in a linear sequence of 18 steps from commercially available compound 11. The synthetically challenging bicyclo[4.4.1] A/B ring system with a strained bridgehead (anti-Bredt) double bond of cyclocitrinol was constructed efficiently and diastereoselectively via a type II intramolecular [5 + 2] cycloaddition.
The asymmetric total synthesis of an unusual C25 steroid containing a unique bicyclo[4.4.1]undecene A/B ring system, resulting in the synthesis of cyclocitrinol (1) and its isomer 8,14 -cyclocitrinol (38), is reported. Initial attempts to construct the synthetically challenging bicyclo[4.4.1]undecene A/B ring system using a type II [5+2] cycloaddition showed that a chiral substituent at the allylic position of the alkene (C6, cyclocitrinol numbering) controlled the stereoselective outcome of the cycloaddition reaction. Late-stage migration of the tetrasubstituted C8-C14 double bond in 8,14 -cyclocitrinol ( 38) to obtain cyclocitrinol (1) proved challenging, inspiring an alternative approach. The chiral β-CH 2 OR group on the allylic substituent at C6 played a pivotal role both in controlling the diastereoselectivity of the type II [5+2] cycloaddition and retaining the C6 substituent under lithium-amine conditions.
Rhizing star: A stereoselective synthesis of the fully functionalized macrocyclic core of rhizopodin, a cytotoxic 38‐membered macrolide, has been disclosed. The key steps involve Sharpless epoxidation, Robinson–Gabriel oxazole synthesis, olefin cross‐metathesis, Suzuki coupling, Yamaguchi esterificationn, and Shiina macrolactonization.
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