Demissidine is an indolizidine alkaloid
isolated from several potato
species. A simple synthesis of demissidine stereoisomers and analogues
from a common steroidal sapogenin tigogenin is presented in the paper.
The key intermediate in the synthesis of these compounds is readily
available tigogenoic acid. Its step-by-step transformation to indolizidine
yielded 20R,25R or 20R,25S products while the direct reductive amination
produced the 20S,25R compound (25-epi-demissidine).
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Bis(indolyl)methane derivatives (BIMs) were synthesized in moderate to good yields by
(thio)urea catalyzed electrophilic substitution of indole (2) with various aldehydes 1. Reactions were
performed under conventional and microwave (MW) heating, either using 1,2-dichloroetane as solvent
or without solvent. The procedure using microwave heating was also applied to the synthesis of the
natural products vibrindole A (3n), arsindoline A (3i), arundine (3o) and tris(1H-indol-3-yl)methane
(3j). Additionally, the synthesis of streptindole was carried out via intermediate 3g. This methodology
is well suited for the synthesis of bis(indolyl)methanes: it offers good yields of products, low sensitivity
to moisture and oxygen, high tolerance to different functional groups on the aldehydes such as alkynes
and trimethylsilane, and simplicity in operation
A simple synthesis method of solanidane alkaloids from common steroidal sapogenins was developed. Previously described multi‐step transformations of tigogenin to demissidine (8–12 steps) were shortened to four steps only. The key‐step of the present synthesis was the epimerization at C25 of the lactam intermediate. Different approaches to this reaction, i. e., a classical one via enolate, and a chemoselective umpolung transformation, were thoroughly investigated. The epimerization step is unnecessary if the starting sapogenin has the same configuration at C25 as the target alkaloid because the configuration at C25 (either R or S) remains intact throughout the synthesis. Thus, the related solanidane alkaloids, 12β‐hydroxy‐25‐epi‐demissidine and 5‐epi‐demissidine, were synthesized in the three‐step procedure with retention of configuration at this stereogenic center from rockogenin (25R‐5α‐sapogenin) or sarsasapogenin (25S‐5β‐sapogenin), respectively.
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