Biogenetically Inspired Total Syntheses of <i>Lycopodium</i> Alkaloids, (+)-Flabellidine and (−)-Lycodine

The first asymmetric total synthesis of (+)-flabellidine (<b>2</b>) and the shortest total synthesis of (−)-lycodine (<b>3</b>) were accomplished by a strategy featuring the one-pot construction of a tetracyclic lycodine skeleton from a linear precursor, which was inspired by the biosynthetic consideration of <i>Lycopodium</i> alkaloids

Asymmetric Total Synthesis of Kopsiyunnanine K, a Monoterpenoid Indole Alkaloid with a Rearranged Skeleton

A new monoterpenoid indole alkaloid, kopsiyunnanine K, was isolated from Kopsia arborea. Its intriguing rearranged structure and absolute configuration, which were inferred from spectral data and a possible biosynthetic pathway, were determined on the basis of a 13-step asymmetric total synthesis

Asymmetric Total Synthesis of Kopsiyunnanine K, a Monoterpenoid Indole Alkaloid with a Rearranged Skeleton

A new monoterpenoid indole alkaloid, kopsiyunnanine K, was isolated from Kopsia arborea. Its intriguing rearranged structure and absolute configuration, which were inferred from spectral data and a possible biosynthetic pathway, were determined on the basis of a 13-step asymmetric total synthesis

Identification of Indole Alkaloid Structural Units Important for Stimulus-Selective TRPM8 Inhibition: SAR Study of Naturally Occurring Iboga Derivatives

The iboga alkaloid voacangine (<b>1</b>) has been reported previously to be the first stimulus-selective TRPM8 antagonist. In the present report, a structure–activity relationship (SAR) study is described on the effects of some naturally occurring indole alkaloid analogues on TRPM8 inhibition. Dihydrocatharanthine (<b>10</b>) and catharanthine (<b>11</b>) were found to be inhibitors of TRPM8 activity, and their IC₅₀ values were equivalent to that of BCTC, a potent and representative TRPM8 antagonist. Furthermore, it was shown that the iboga moiety is the most crucial unit for TRPM8 blockade and that its stereostructure, as found in <b>1</b> but not in <b>10</b> and <b>11</b>, is essential for chemical agonist-selective TRPM8 inhibition. These findings should provide useful information for synthesizing additional stimulus-selective and TRPM8-selective blockers

A Cyclopeptide and a Tetrahydroisoquinoline Alkaloid from <i>Ophiorrhiza nutans</i>

A new cyclopeptide, ophiorrhisine A (<b>1</b>), a new tetrahydroisoquinoline alkaloid, 7′,10-dide-<i>O</i>-methylcephaeline (<b>2</b>), two known β-carboline alkaloids, and four known tetrahydroisoquinoline alkaloids were isolated from <i>Ophiorrhiza nutans</i> (Rubiaceae). Compound <b>1</b> is a tetrapeptide possessing a 14-membered paracyclophane ring and a novel <i>N,N,N-</i>trimethyltyrosine residue in the side chain. The stereochemistry at the aryl–alkyl ether bond was different from that of other known 14-membered paracyclophanes. The structure of <b>2</b> was established by spectroscopic analysis and semisynthesis

Asymmetric Total Synthesis of an Iboga-Type Indole Alkaloid, Voacangalactone, Newly Isolated from <i>Voacanga africana</i>

A new hexacyclic iboga-type indole alkaloid, voacangalactone (<b>1</b>), was isolated from <i>Voacanga africana</i>, and its structure including the absolute configuration was established by asymmetric total synthesis involving such key steps as the asymmetric Diels–Alder reaction using an aminodiene and the construction of an isoquinuclidine ring and an indole skeleton

Asymmetric Total Synthesis of Novel Pentacyclic Indole Alkaloid, Kopsiyunnanine E, Isolated from <i>Kopsia arborea</i>

A new pentacyclic indole alkaloid, kopsiyunnanine E, was isolated from Yunnan <i>Kopsia arborea</i>, and its structure, which was inferred from spectroscopic data, was established by a 16-step asymmetric total synthesis that proved that the natural alkaloid was not enantiomerically pure