Enantioselective Total Synthesis of the Melodinus Alkaloid (+)‐Meloscine

Abstract

Enantioselective synthesis in a new light: The template‐controlled [2+2] photocycloaddition leading to product 1 is the first example of this type of reaction in natural product synthesis. In addition, a retro‐benzilic acid rearrangement (→2), a Claisen rearrangement (→3), and a ring‐closing metathesis played decisive roles in the synthesis of the alkaloid (+)‐meloscine (4).

Phytochemical and Pharmacological Properties of the Genus Melodinus – A Review

“…This first type included nineteen alkaloids (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) ( Table 1, Figure 1) . The common characteristic compounds, venalstonine (3) and venalstonine (7) were produced by more than fifteen Melodinus species.…”

“…Current crude alkaloid mixtures and purified alkaloids from some Melodinus species have demonstrated antitumor and antibacterial activities [6,7]. Many characteristic melodinus alkaloids, such as meloscine, epimeloscine, scandine and vincadifformine, had for a long time attracted great interest of synthetic organic chemists as challenging targets due to their marked diversity and complicated architectures [8,9,10] And more than twenty alkaloids were reviewed from the genus Melodinus by Sevenet et al [11]. About 14 alkaloids can be classified into the melodan skeleton and its rearranged version and derived from 18, 19-didehydrotabersonine as parent compound in the plant family Apocynaceae [12] Recently, much attention has been paid to Melodinus plants to search active melodinus alkaloids.…”

Hypervalent iodine reagents in the total synthesis of natural products

“…ROAc, 215 ROPiv, 92,226 ArOMe, 194,230,232,233,236,239,241,242 ArOBn, 131,242 ArOAllyl, 125 ArOMOM, 131,233 ArOAc, 232 methylenedioxy 131,242 ArOEOM, 241 and R 2 NBoc. 194,229,243 EOM: ethoxymethyl IBX is not soluble in many organic solvents and the typical oxidation takes place in DMSO at room temperature. [220][221][222][223] However, the oxidation of alcohols with IBX has been described using other procedures.…”

Recent developments in syntheses of the post-secodine indole alkaloids. Part III: Rearranged alkaloid types

“…Removal 17,18 of the Boc-group in (+)-963 with TFA and an exposure to hydrogen over Pearlman's catalyst Pd(OH) 2 caused hydrogenolysis, reduction of the enol acetate as well as an intramolecular reductive amination; after Boc-reprotection, the carbamate (+)-964 was isolated as a single diastereoisomer in 78% yield, Scheme 4. The following 4-step transformation to allyl alcohol 966 (60% overall) set the stage for an ortho-Claisen rearrangement, which was effected by heating with excess trimethyl orthoacetate and proceeded with only moderate diastereoselectivity (85%; 967a:967b 7:3).…”