Collective Asymmetric Total Synthesis of C‐11 Oxygenated Cephalotaxus Alkaloids

Abstract

While numerous studies pertaining to the total synthesis of Cephalotaxus alkaloids have been reported, only two strategies have been reported to date for the successful synthesis of the C‐11 oxygenated subset, due to the additional synthetic challenge posed by the remote C‐11 stereocenter. Herein, we report the collective asymmetric total synthesis of C‐11 oxygenated Cephalotaxus alkaloids using a chiral proline both as a starting material and as the only chirality source. A tetracyclic advanced intermediate was synthesized in a highly stereoselective manner from l‐proline in 8 steps involving sequential chirality transfer steps such as a diastereoselective N‐alkylation, stereospecific Stevens rearrangement and intramolecular Friedel–Crafts reaction via an unusual O‐acyloxocarbenium intermediate. From a common intermediate, the asymmetric total synthesis of six C‐11 oxygenated Cephalotaxus alkaloids was completed by a series of oxidation state adjustments.

Bioecology, landscape use, and breeding technology of ephalotaxus drupacea sieb. Et zucc.

“…The Cephalotaxus species typically grow in humid and warm shaded mountains, at elevations ranging from 300 to 3300 meters above sea level, mixed with other forest trees. In 1955, during a visit to the Tashkent Botanical Garden, an introduction was made to the Cephalotaxus species [4][5][6][7]. The family's species are known for their rich alkaloid composition, which has been widely studied by foreign researchers.…”

“…Zarnab grows well, mainly in shade and semi-shade, forming a second layer under trees. Shade-tolerant, shade-loving [1][2][3][4][5][6][7].…”

“…Despite 3.2 million hectares of forest in the country, which is 7% of the total area, only 821 thousand hectares are cultivated forests, meaning that only 2% of the country's territory is covered with forests. Planting and cultivating various ornamental shrubs is important for the natural reproduction of forests, as natural forests are rare in the country [5][6][7][8][9]. The UN Convention on Biological Diversity has identified 34,000 plant species that are under threat of extinction.…”

Natural product total synthesis using rearrangement reactions

“…Kim's group used simple L-proline as the starting material for the total synthesis of torreyafargesine A (65). 20 The key to the success of the synthesis was using a Stevens rearrangement to set up the requisite stereogenic center. L-Proline was transformed into bicycle 66, which underwent diastereoselective alkylation with 67 and subsequent Stevens rearrangement to afford 68.…”