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[ASAP] Sequential Norrish–Yang Cyclization and C–C Cleavage/Cross-Coupling of a [4.1.0] Fused Saturated Azacycle
[ASAP] Concise Chemoenzymatic Synthesis of Fasamycin A
[ASAP] Leptosperols A and B, Two Cinnamoylphloroglucinol–Sesquiterpenoid Hybrids from Leptospermum scoparium: Structural Elucidation and Biomimetic Synthesis
[ASAP] Nucleophile-Dependent Z/E- and Regioselectivity in the Palladium-Catalyzed Asymmetric Allylic C–H Alkylation of 1,4-Dienes
Branched‐Selective Direct α‐Alkylation of Cyclic Ketones with Simple Alkenes
An intermolecular direct branched‐selective α‐alkylation of cyclic ketones has been achieved using simple alkenes as the alkylation agents. 7‐Azaindoline is employed as a bifunctional ligand to facilitate enamine formation and guide subsequent C−H activation with an iridium catalyst. This method offers a straightforward and byproduct‐free means to access ketones with β‐stereocenters.
Abstract
Herein, we describe an intermolecular direct branched‐selective α‐alkylation of cyclic ketones with simple alkenes as the alkylation agents. Through an enamine‐transition metal cooperative catalysis mode, the α‐alkylation is realized in an atom‐ and step‐economic manner with excellent branched selectivity for preparing β‐branched ketones. Employment of a pair of bulky Brønsted acid and base as additives is responsible for enhanced efficiency. Promising enantioselectivity (74 % ee) has been obtained. Experimental and computational mechanistic studies suggest that a pathway through alkene migratory insertion into the Ir−C bond followed by C−H reductive elimination is involved for the high branched selectivity.
Total Synthesis and Conformational Study of Callyaerin A: Anti-Tubercular Cyclic Peptide Bearing a Rare Rigidifying (Z)-2,3- Diaminoacrylamide Moiety
Abstract
The first synthesis of the anti-TB cyclic peptide callyaerin A (1), containing a rare (Z)-2,3-diaminoacrylamide bridging motif, is reported. Fmoc-formylglycine-diethylacetal was used as a masked equivalent of formylglycine in the synthesis of the linear precursor to 1. Intramolecular cyclization between the formylglycine residue and the N-terminal amine in the linear peptide precursor afforded the macrocyclic natural product 1. Synthetic 1 possessed potent anti-TB activity (MIC100=32 μm) while its all-amide congener was inactive. Variable-temperature NMR studies of both the natural product and its all-amide analogue revealed the extraordinary rigidity imposed by this diaminoacrylamide unit on peptide conformation. The work reported herein pinpoints the intrinsic role that the (Z)-2,3-diaminoacrylamide moiety confers on peptide bioactivity.
A rigid structure: Callyaerin A, an anti-tuberculosis macrocyclic peptide containing a rare (Z)-2,3-diaminoacrylamide moiety, was synthesized in high yield using an uncommon building block, Fmoc-formylglycine-diethylacetal. Variable-temperature NMR studies revealed the high conformational rigidity that the (Z)-2,3-diaminoacrylamide moiety confers on peptide structure, thus highlighting its potential as a novel structural element for conformation constraints.