Total Synthesis of (−)-Histrionicotoxin 285A and (−)-Perhydrohistrionicotoxin

Abstract

Starting from commercially available ( S)-glycidol, and via a common intermediate, the total synthesis of (-)-histrionicotoxin 285A and (-)-perhydrohistrionicotoxin has been achieved. Key to this synthesis was the efficient construction of a six-membered, chiral, cyclic nitrone.

Synthesis of Phosphonoglycine Backbone Units for the Development of Phosphono Peptide Nucleic Acids

“…After silylation of 13 at the primary position, [23] the resulting protected epoxide derivative 14 (which can also be obtained by kinetic resolution [24] or by asymmetric epoxidation) [25] underwent noticeable decomposition during its ring opening to azido alcohol 15 (Scheme 3), and only a marginal quantity of the expected compound (ca 3 %) could be isolated. Pleasingly, the replacement of 13 with (S)-1,2-isopropylideneglycerol [(S)-Solketal, 16] as starting material led to much improved results in terms of isolated yields.…”

“…(S)-3-Azido-1-(tert-butyldiphenylsilyloxy)-2-propanol (15): Method (a) from (R)-glycidol: (R)-glycidol (Sigma-Aldrich, 13) was conventionally silylated [23] to furnish 14 as an oil in ca. 90 % yield after chromatography (gradient, hexane/Et 2 O 10:0.5 Ǟ 10:1.…”

Stereoselective Cycloaddition Reactions

“…Phenyl and 2-thiophenyl groups were tolerated at the C2 position among several aryl groups examined, and removal of the C7-aryl group did not affect the naphthyridinone's EC activation (Figure 16 64 and central neuronal nicotine acetylcholine receptors. 67,68 For the synthesis of (À)-HTX, acetylenic diol 98 was elaborated to hydroxylamine 99 through diastereoselective introduction of a hydroxylamine group. 66 Total synthesis of (À)-HTX 106 and (À)-perhydrohistrionicotoxin 107 has been achieved by using a sequence of cycloaddtion/retro-cycloaddition/cycloaddition reactions (Scheme 16.15).…”

“…68 The tricycle 105b was converted into (À)-perhydrohistrionicotoxin 107 in a seven-step reaction sequence (Scheme 16.15).…”

Palladium‐Catalyzed Coupling Reactions of Thioimidate N‐Oxides: Access to α‐Alkenyl‐ and α‐Aryl‐Functionalized Cyclic Nitrones

“…[3] Cyclic nitrones have mainly been used in synthetic approaches towards natural products and biologically active compounds. [4] In those multistep syntheses the most recent methods involved carbohydrate templates.…”