Total Syntheses of (±)-β-Erythroidine and (±)-8-oxo-β-Erythroidine by an Intramolecular Diels−Alder Cycloaddition of a 2-Amidoacrolein

Abstract

[reaction: see text] The total syntheses of (+/-)-beta-erythroidine and (+/-)-8-oxo-beta-erythroidine are described. The tetracyclic ring system of the natural products was quickly assembled by a strategy that features a retrocycloaddition/cycloaddition reaction of an amidodioxin, an intramolecular Heck reaction, and a 6pi-electrocyclic ring closure of a dienoic acid.

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

“…Despite the relatively harsh reaction conditions, aldehyde 135-9 was isolated in 64% yield and advanced to strychnine in only four additional steps. 500 Other applications of intramolecular [4 + 2] cycloadditions for the construction of stereogenic C−N bonds can be found in the total synthesis of (±)-β-erythroidine and (±)-8-oxo-βerythroidine (an enamide as the dienophile) 501 and the vindoline domain of (+)-vinblastine (an imine as the dienophile, 2-(2-indolyl)acrylate as the diene). 502 Intermolecular [4 + 2] cycloadditions have been applied in the total synthesis of quinolizidine nupharamine alkaloids from castroleum (3-furanaldimine as the dienophile), 503 the dihydroquinoline alkaloid (±)-martinelline from the tropical plants Martinella (dihydropyrrolidine as the dienophile), 504 and benzodioxazine alkaloids phellodonin and sarcodonin ε from the fungus Phellodonin niger, which possess a truly bizarre molecular functionalization (piperazine N,N′-dioxide as the heterodienophile).…”

Photocatalytic Umpolung ofN- andO-substituted alkenes for the synthesis of 1,2-amino alcohols and diols

“…1,2 Alkynes are highly useful building blocks for synthesis, as starting points for product diversication. 3 Combining both functionalities, 1-alkynyl-1,2-amino alcohols can be found as intermediates in the synthesis of insecticidal 4-alkynyloxazolines 4 and b-erythroidine, 5,6 as well as essential structural elements in bioactive antitumoral enediynes. 7,8 1-Alkynyl-1,2-diols can be found, for example, in the Petrosiol family of neurotrophic diyne tetraols.…”

α-Functionally Substituted α,β-Unsaturated Aldehydes as Fine Chemicals Reagents: Synthesis and Application

“…Such compounds are known to be excellent dienophiles for Diels–Alder reactions and subsequent design of bioactive natural compounds [ 77 , 78 ]. The products of Diels–Alder cycloaddition reactions of 2-amidoacroleins with dienes are structural motifs of biologically active tricyclic alkaloids (cytotoxins lepadiformine, fasicularin, cylindricines A/B) [ 79 , 80 , 81 , 82 ] and immunosuppressent FR901483 [ 83 ].…”