The synthesis of (+)-preussin and related pyrrolidinols by diastereoselective Paternò-Büchi reactions of chiral 2-substituted 2,3-dihydropyrroles.
The N-alkoxycarbonyl substituted 2,3-dihydropyrroles 3 and 8 are converted to 2-benzyl-3-pyrrolidinols by the Paternò - Büchi reaction followed by hydrogenolysis. Since the addition of the photoexcited benzaldehyde at the unsaturated heterocycle proceeds in a syn fashion, the benzyl group at C-2 and the hydroxy group at C-3 of the product are cis oriented. The simple and facial diastereoselectivities of the Paternò-Büchi reaction were studied more closely and the relative configuration of the products was elucidated. The thermodynamically less stable endo product is formed as a result of simple diastereoselection. The face differentiation in 2-substituted 2,3-dihydropyrroles is presumably due to the nonplanarity of these heterocycles, which forces attack of the carbonyl group on the face with the existing substituent. All-cis-pyrrolidinols are consequently formed after hydrogenolysis. Following this route, a total synthesis of the pyrrolidinol alkaloid (+)-preussin (1) was conducted, which yielded the target compound in a total yield of 11% over nine steps starting from L-pyroglutaminol (11).
Bach
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T
Fachbereich Chemie der Philipps-Universität, Marburg, Germany. thorsten.bach@ch.tum.de
Brummerhop
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H
Harms
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K
D000841:Anisomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001235:Aspergillus ochraceus / Q000737:chemistry*; D006859:Hydrogen / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000935:Antifungal Agents; C098358:FR 901483; D007166:Immunosuppressive Agents; D009943:Organophosphorus Compounds; D011758:Pyrroles; D011759:Pyrrolidines; C058280:preussin; D000841:Anisomycin; D006859:Hydrogen