Synthesis of (5R,8S,10R)-6-(Allyloxy)- and (5R,8S,10R)-6-(Propyloxy)ergolines from the 6-Methyl Precursors

Novel (5R,8S,10R)-6-(allyloxy)- and (5R,8S,10R)-6-(propyloxy)ergolines have been synthesized by use of a Meisenheimer [2,3]-sigmatropic rearrangement of a (5R,8S,10R)-6-allyl-ergoline N⁶-oxide as key step.     

Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators

[structures: see text] Both (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)benzolactam-V8 were designed and synthesized as PKC modulators. Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKC alpha.     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

Concise asymmetric synthesis of (5S, 6S)- aeginetolide and (5S)- dihydroactinidiolide

An asymmetric deprotonation reaction allows for short syntheses of the lactones (5S, 6S)- Aeginetolide (1) and (5S)-Dihydroactinidiolide (2).     

Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)-(6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C

[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.     

Synthesis of (2S,4S)- and (2S,4R)-5-fluoroleucine and (2S,4S)-[5,5-2H2]-5-fluoroleucine

Syntheses of (2S,4S)- and (2S,4R)-5-fluoroleucine, and, and of (2S,4S)-[5,5-(2)H(2)]-5-fluoroleucine, have been completed. The methodology allows these compounds to be prepared in sufficient quantities for incorporation by solid-state protein synthesis into strategic sites in proteins for folding studies. X-ray structures of the epimers and have been obtained and show the presence of conformational isomerism. The torsion angles between the F-C bond and the main chain are compared with values found in a mutant of the protein ubiquitin in which (2S,4S)-5-fluoroleucine replaces leucine residues 50 and 67 in the native protein.     

Synthesis of (5R)- and (5S)-5-Methyl-5, 6-dihydrouridine Derivatives

The hydrogenation of 2′, 3′-O-isopropylidene-5-methyluridine (1) in water over 5% Rh/Al₂O₃ gave (5 R)- and (5 S)-5-methyl-5, 6-dihydrouridine (2) , separated as 5′-O-(p-tolylsulfonyl)- (3) and 5′-O-benzoyl- (5) derivatives by preparative TLC. on silica gel and ether/hexane developments. The diastereoisomeric differentiation at the C(5) chiral centre depends upon the reaction media and the nature of the protecting group attached to the ribosyl moiety. The synthesis of iodo derivatives (5 R)- and (5 S)- 4 is also described. The diastereoisomers 4 were converted into (5 R)- and (5 S)-2′, 3′,-O-isopropylidene-5-methyl-2, 5′-anhydro-5, 6-dihydrouridine (7) .     

Enantioselective synthesis of methyl (5Z,8S)-8,9-epoxynon-5-enoate, an eicosanoid synthon

A six-step synthesis of methyl (5Z,8S)-8,9-epoxynon-5-enoate, a known synthon of constanolactones and hepoxilins, from 5-hexynoic ester was developed. The enantiomeric purity of the synthon was attained by S-enantiodirected dihydroxylation of a double bond in the intermediate methyl non-8-en-5-ynoate with subsequent enantioselective hydrolysis of the epoxide group in the admixture of the minor R-enantiomer. Dedicated to Academician V. A. Tartakovsky on his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1586–1592, August, 2007.     

Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

The enantioselective synthesis of (4S,5S)- and (4S,5R)-5-hydroxy-4-decanolide,the autoregulators from Strepotomyces griseus

(4S, 5S)- and (4S, 5R)-5-Hydroxy-4-decanolide ( 1a and 1b ), the proposed autoregulators from Strepotomyces Griseus were synthesized from a propargyl alcohol 2 in an overall yield of 30%, employing the Sharpless asymmetric epoxidation as the key step.