Total Synthesis of (+)-Gregatin B and E

Abstract

The first total synthesis of (+)-gregatin E and a new total synthesis of (+)-gregatin B are described. Key features of our synthetic approach involve a palladium-catalyzed cyclization-methoxycarbonylation of optically active propargylic acetate and a Suzuki-Miyaura coupling or CuTC-mediated coupling reaction. The absolute configuration of (+)-gregatin E (5R,5'S) is proposed.

Asymmetric Dihydroxylation of Esters and Amides of Methacrylic, Tiglic, and Angelic Acid: No Exception to the Sharpless Mnemonic!

“…To the best of our knowledge, the trisubstituted C=C bond of angelic acid esters 3 (Figure 1), and derivatives thereof, is the only SAD site at which, according to the literature, configurational control was incongruent, at least in one instance contradictory, and in part in conflict with the Sharpless mnemonic (Scheme , see below) 11–19. This investigation unravels the steric course of the SAD of esters and amides of methacrylic acid,20 tiglic acid,21 and angelic acid22 unambiguously (see below); enantiomerically pure (in most cases) or enriched (occasionally) 1,2‐diols obtained from such substrates were used in the construction of complex natural products,20k,21b,21c represented drug candidates,20h,20j served as building blocks for peptides [20a,20c,20e–20g,21a,22b] or became the progenitor of other diverse products. [20b,20d,20i,21d,22a,22c] Our central finding was that angelate SADs proceed in full accordance with the Sharpless mnemonic.…”

“…The methyl ester containing diol 23a and its progenitors 23b – e are R enantiomers37 because the absolute configuration of the SAD‐based Weinreb amide 23d is known 20a,20c,20f,20k. The methyl ester containing diol syn ‐ 7a and its progenitors 7b – e are 2 R ,3 S ‐configured because this is the absolute configuration of the carboxylic acid obtained by hydrolysis of this syn ‐diol; this configuration was established by X‐ray structural analysis of an enzyme complex of that acid 21d.…”

Total Synthesis of the Death Cap Toxin Phalloidin: Atropoisomer Selectivity Explained by Molecular‐Dynamics Simulations

“…After Sharpless ADH and silylation of the diol group with TBDMS, compound 15 was obtained in 65 % yield with 90 % ee . Subsequent to reduction with LiAlH 4 , aldehyde 16 was used in a Horner–Wadsworth olefination to form dehydroamino acid ester 17 . The protected dihydroxy‐Leu derivative 17 was stereoselectively hydrogenated using with Ru(COD) 2 BF 4 and ( R )‐MonoPhos as a ligand .…”

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

“…A Pd coupling reaction between vinyl iodide 116 and 2-((E)but-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 117 provided 114 in 80% yield (Scheme 21). [92] SCHEME 17 Total Synthesis of (-)-Goniomitine Dihydrocodeine 118 is a semi-synthetic opioid compound, which is prescribed for severe pain after surgery in hospital or as an antitussive in small amount with acetoaminophene (paracetamol) or acetyl salicylic acid (aspirin). It was first developed from morphine, isolated from opium in Germany in 1908 and first marketed in 1911.…”