An asymmetric synthesis of (+)-kjellmanianone

Racemic and asymmetric syntheses of kjellmanianone, a novel cyclopentenoid antibiotic, are described.     

Formal asymmetric synthesis of (+)-tofacitinib

Tofacitinib is an efficient and selective Janus kinase 3 (JAK3) inhibitor, and is used as an immunosuppressant drug for the treatment of rheumatoid arthritis and transplant patients. Herein we report a concise formal asymmetric synthesis of tofacitinib from homochiral 1,3-dioxolanone 10b, which was elaborated through a highly stereoselective Michael addition followed by solvent-free removal of the chiral auxiliary and ring cyclization to furnish chiral imide 8. The preparation of tofacitinib’s precursor 16 could be obtained after reduction of 8 followed by sequential oxidation, reductive amination and S_NAr reactions.     

An asymmetric synthesis of (+)-desoxoprosophylline

An efficient synthesis of (+)-desoxoprosophylline is described. The key steps in the reaction sequence include the preparation of an N-Cbz-sulfilimine from the corresponding sulfoxide using the Burgess reagent, regio- and stereoselective hetero-functionalization of an alkene using the pendant sulfilimine as the nucleophile and a stereoselective amidomercuration to form the cis-2,6-disubstituted piperidine ring.     

An asymmetric synthesis of (+)-monomorine I

The synthesis of (+)-monomorine I, an indolizidine alkaloid isolated from Monomorium pharaonis, has been achieved. The 2,6-cis-piperidine ring moiety of (+)-monomorine I was constructed using diastereoselective aminopalladation. Chain elongation via cross-metathesis using Hoveyda-Grubbs 2nd catalyst followed by deprotection of the Cbz group and cyclic reductive hydroamination afforded (+)-monomorine I.     

A six-step asymmetric synthesis of (+)-hyperaspine

[reaction: see text] The ladybird alkaloid, (+)-hyperaspine, has been synthesized in a concise and highly stereoselective manner. The total synthesis was accomplished in six steps and 21% overall yield.     

A total asymmetric synthesis of (+)-ar-turmerone

Employing a chiral oxazoline, a total synthesis of the title compound is described.     

A facile asymmetric synthesis of (+)-eldanolide

The monoterpenoid pheromone (+)-eldanolide, a long range sex attractant, has been synthesized in four steps from the chiral 2,3-epoxy alcohol 4 in 36% overall yield. Our synthetic strategy features the formation of a 1,3-diol by regio- and stereoselective ring opening of 2,3-epoxy alcohol 4, an intermediate easily available from Sharpless asymmetric epoxidation. Other key steps include one carbon elongation, saponification, and lactonization. The present work constitutes a general method for the rapid synthesis of a number of related γ-lactone natural products.     

First asymmetric total synthesis of (+)-sparteine

[reaction: see text] The total synthesis of (+)-sparteine was accomplished from 2,5-norbornadione in 15 steps and 15.7% overall yield. The key steps were two ring-expansion reactions, one involving an intramolecular Schmidt reaction and one using a novel variant of the photo-Beckmann rearrangement.     

Catalytic asymmetric total synthesis of (+)-lactacystin

Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor, was accomplished using a catalytic enantioselective Strecker reaction of a ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was selected as a stable masked alpha-hydroxy ketoimine analogue. Excellent enantioselectivity (98% ee) and practical catalyst activity were produced under the optimized catalyst preparation method using 2.5 mol % Gd{N(SiMe3)2}3 as a metal source and 3.8 mol % D-glucose-derived ligand 8. This reaction was conducted on a 5 g scale. The chiral tetrasubstituted C-5 carbon efficiently controlled the stereochemistry of the other three chiral centers of lactacystin. Chelation-controlled Meerwein-type reduction of ketone 5 using i-PrMgBr (originally reported by Kang in a related substrate) selectively produced the desired secondary alcohol at the C-9 position. The C-6 hydroxy and C-7 methyl groups were introduced via a silyl conjugate addition followed by the Tamao oxidation and Donohoe methylation, respectively, in a highly stereoselective manner. A practical amount of enantiomerically pure clasto-lactacystin beta-lactone (2), the biologically active form of (+)-lactacystin, can be synthesized using this route. clasto-Lactacystin beta-lactone (2) was converted to (+)-lactacystin following the reported procedure.     

Catalytic asymmetric total synthesis of (+)-yohimbine

The total synthesis of (+)-yohimbine was achieved in 11 steps and 14% overall yield. The absolute configuration was established through a highly enantioselective thiourea-catalyzed acyl-Pictet-Spengler reaction, and the remaining 4 stereocenters were set simultaneously in a substrate-controlled intramolecular Diels-Alder reaction.     

First asymmetric total synthesis of (+)-curcutetraol

The first asymmetric total synthesis of (+)-curcutetraol, a marine phenolic bisabolane-type sesquiterpene, was achieved in eight steps in ca. 50% overall yield. The chiral tertiary benzylic alcohol moiety in the o-position of a phenol was constructed in high optical yield (99% ee) by an asymmetric synthesis using a chiral aminal, (2R,5S)-2-methoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane.     

Efficient asymmetric synthesis of (+)-SCH 351448

An efficient and stereocontrolled total synthesis of (+)-SCH 351448, a novel activator of low-density lipoprotein receptor promoter, has been achieved with a longest linear sequence of 21 steps. Key steps include applications of the recently developed asymmetric allyl- and crotylsilane reagents and a new protodesilylative version of the tandem silylformylation/allylsilylation reaction, which provides an efficient synthesis of 1,5-syn-diols. [reaction: see text]     

Chiral diamines for asymmetric synthesis: an efficient RCM construction of the ligand core of (−)- and (+)-sparteine

An efficient RCM-based approach was applied to the total asymmetric synthesis of a tricyclic diamine and, formally, of its enantiomer, widely known as efficient and versatile chiral ligands of the sparteine-like type.     

A concise asymmetric total synthesis of (+)-brevisamide

A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide.     

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H has been achieved. Key step involved construction of all-carbon quaternary carbon by palladium-catalyzed conjugate addition of arylboronic acid to 3-methyl cyclohexenone. Furthermore, a new approach to build [6-5-6] tricyclic backbone via formyl introduction and subsequent aldol-type condensation was also explored.     

Efficient total synthesis of (+)-curcuphenol via asymmetric organocatalysis

The catalytic enantioselective synthesis of (+)-curcuphenol is described herein. This approach involves the use of an organocatalytic alkylation of m-anisidine, a diazotation/Sandmeyer reaction of the amine and a Negishi-type coupling with dimethylzinc. This versatile strategy allows for the rapid synthesis of other members of this class of natural products.     

A short asymmetric synthesis of (+)-lyoniresinol dimethyl ether

A short, efficient synthesis of the lignan (+)-lyoniresinol dimethyl ether is described. The synthesis is achieved by asymmetric photocyclization of an achiral dibenzylidenesuccinate to a chiral aryldihydronaphthalene. (-)-Ephedrine is used as a chiral auxiliary to bias the atropisomeric equilibrium in the dibenzylidenesuccinate prior to the photochemical reaction. The synthesis of the title compound was accomplished in five steps, and the final product was recrystallized to constant melting point and rotation.     

Versatile asymmetric synthesis of the kavalactones: first synthesis of (+)-kavain

[reaction: see text] Three asymmetric pathways to the kavalactones have been developed. The first method is chiral auxiliary-based and utilizes aldol reactions of N-acetyl thiazolidinethiones followed by a malonate displacement/decarboxylation reaction. The second approach uses the asymmetric catalytic Mukaiyama additions of dienolate nucleophile equivalents developed by Carreira and Sato. Finally, tin-substituted intermediates, prepared by either of these routes, can serve as advanced general precursors of kavalactone derivatives via Pd(0)-catalyzed Stille couplings with aryl halides.