Asymmetric Total Synthesis of the 1-epi-Aglycon of the Cripowellins A and B

Abstract

[structure: see text] The unusual [5.3.2]-bicyclic structure of the insecticidal Amaryllidaceae alkaloids cripowellin A (1) and B (2) has been synthesized for the first time via a sequence of Sharpless dihydroxylation, ring-closing metathesis, and intramolecular Heck reaction. The asymmetric synthesis of the 1-epi-aglycon 82 proceeds with virtually complete diastereo- and enantioselectivity (de, ee > or = 98%) in 13 steps and an overall yield of 5.6%. In addition, three alternative approaches toward the aglycon 3 are also described focusing on (1) the alkylation of the 2-benzazepinedithianes 35 and 36 with the electrophile 11, (2) a radical cyclization of the precursor (R/S,S,S)-39, and (3) an intramolecular arylation reaction of the aryl ketone 47.

Alkaloid Diversity in Galanthus elwesii and Galanthus nivalis

“…In contrast to the extensive chemo-ecological studies on the pyrrolizidine and quinolizidine alkaloids in the genera Senecio [32] and Lupinus [20], respectively, there are only few reports regarding the interactions between herbivores, and plants or alkaloids of the family Amaryllidaceae [33] [34]. Taking into account the known biological activity of the compounds dominating the alkaloid fractions of the populations, we could suggest that natural selection leads to accumulation of different alkaloids with potent pharmacological and biological activities that participate in defense system.…”

Synthesis of an Acyclic C1–C11 Fragment of Peloruside B

“…A onestep protection gave the 2,3-acetonide dimethyl ester, [20,21] which was then reduced [22] to provide diol 6. Mono protection of one alcohol with tBuMe 2 SiCl [23] followed by iodination [24] of the remaining hydroxy group gave 7 in an excellent 67 % overall yield over the four steps. Treatment of iodo 7 with the lithium anion of 1,3-dithiane produced dithiane 8, [24] which was then further lithiated and treated with ethylene oxide formed in situ from 2-bromoethanol to form alcohol 9.…”

“…Mono protection of one alcohol with tBuMe 2 SiCl [23] followed by iodination [24] of the remaining hydroxy group gave 7 in an excellent 67 % overall yield over the four steps. Treatment of iodo 7 with the lithium anion of 1,3-dithiane produced dithiane 8, [24] which was then further lithiated and treated with ethylene oxide formed in situ from 2-bromoethanol to form alcohol 9. Finally, Swern oxidation of 9 provided aldehyde 3 in an overall yield of 24 % over seven steps.…”

“…Accurate masses were recorded on Mariner time-of-flight spectrometers. Compounds 6, [20][21][22] 7, [23,24] and 8 [24] were synthesized as described previously and spectroscopic data matched that of previously published spectra.…”

Studies toward the total synthesis of cyclodidemniserinol trisulfate. Part II: 3,5,7-Trisubstituted 6,8-dioxabicyclo [3.2.1] octane core structure construction via I2-mediated deprotection and ring closure tandem reaction

“…a b s t r a c t The 3,5, octane core structure was synthesized by employing a chiral pool convergent synthesis strategy and the I 2 -mediated simultaneous deprotection and ring closure reaction as the key step, providing a practical and efficient synthetic approach applicable to the further total synthesis of the natural product cyclodidemniserinol trisulfate.…”