- Baker's Yeast Reductions of β-Oxopyrrolidinecarboxylates: Synthesis of (+)-cis-(2R,3S)-3-Hydroxyproline and (-)-(1S,5S)-Geissman-Waiss Lactone, a Useful Precursor to Pyrrolizidine Alkaloids
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Baker's yeast reduction of the β-oxo proline derivative 5 leads to the cis-hydroxy ester 6 and thence to (+)-cis-(2R,3S)-3-hydroxyproline 7, with >90percent enantiomeric enrichment.Subsequent one-carbon homologation leads to the (-)-Geissman-Waiss lactone
- Cooper, Jeremy,Gallagher, Peter T.,Knight, David W.
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- Expedient Synthesis of (+)-cis-(2R,3S)-3-Hydroxyproline and (-)-(1S,5S)-2-Oxa-6-azabicyclo octan-3-one (The Geissman-Waiss Lactone): Formal Enantioselective Syntheses of (-)-Retronecine and Related Pyrrolizidine Alkaloids
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Yeast reduction of the keto-proline (5) affords the hydroxyproline derivative (6) (diastereoisomeric excess > 99percent cis; enantiomeric excess, e.e., 80percent(; subsequent hydrolysis and crystallization gives (+)-cis-(2R,3S)-3-hydroxyproline (7) (93percent e.e.) which has been homologated to the bicyclic lactones (10) and (11), precursors of (-)-retronecine, (+)-platynecine, (-)-croalbinecine and related pyrrolizidines.
- Cooper, Jeremy,Gallagher, Peter T.,Knight, David W.
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- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1, 2-A]PYRIDINE-3- CARBOXAMIDE COMPOUNDS AS CFMS INHIBITORS
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Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.
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Page/Page column 111
(2011/07/09)
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- 184. Total synthesis of cyclothialidine
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A total synthesis of cyclothialidine (1), a new DNA gyrase inhibitor isolated from Streptomyces filipinensis, is described The synthetic concept was tested by preparing the lactone 13 (Scheme 2) which contains the characteristic bicyclic core entity of 1. Key features of the synthesis of 1 are: preparation of 3,5-dihydroxy-2,6-dimethylbenzoic acid (23) from 3,5-dihydroxybenzoic acid (19) by two consecutive Mannich aminomethylation/hydrogenation sequences; benzylic N-bromosuccinimide bromination of an ester derivative 25 thereof and its subsequent coupling with Boc-Ser-Cys-OMe (11); cyclization of the ω-hydroxy acid 29 to the 12-membered lactone 30 using preferably Mitsunobu conditions; completion of the peptidic side chains of 1 using Boc strategy (Scheme 4) Optically pure cis-N-(tert-butoxycarbonyl)-3-hydroxy-L-proline ((-)-14) was obtained by resolution of the racemate via an efficient reaction sequence containing a lipase-catalyzed enantiospecific acetate hydrolysis (Scheme 3). The structure of natural 1 was confirmed by comparison with the synthetic material. The synthetic route described provides also easy access to analogues of 1, e.g., via the intermediate 30.
- Goetschi, Erwin,Jenny, Christian-Johannes,Reindl, Peter,Ricklin, Fabienne
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p. 2219 - 2234
(2007/10/03)
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