Abstract
Among the most structurally remarkable guanidine natural products are the crambescidin/ptilomycalin A family of marine alkaloids. The evolution of a practical strategy for preparing pharmacologically significant crambescidin/ptilomycalin A alkaloids that lack oxidation at C13 is described. The first total syntheses of crambescidin 800 (2), crambescidin 657 (6), and neofolitispate 2 (7) are reported in full detail. The central strategic step in these convergent total syntheses is tethered Biginelli condensation of β-keto ester 24 with ureido aminal 61 to combine all carbons of the guanidine nucleus and set the pivotal C10−C13 stereorelationship. The total synthesis of crambescidin 800 (2) was accomplished in 3% overall yield from commercially available 3-butyn-1-ol by way of 16 isolated and purified intermediates. Full details of our earlier total synthesis of ptilomycalin A (1) are also presented. The total syntheses described in this disclosure confirm the stereochemical assignments of 1, 2, 6, and 7 and rigorously establish that the absolute configuration of the hydroxyspermidine side chain of crambescidin 800 (2) is S.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
