Synthesis of (+)-goniopypyrone and (+)-goniotriol using Pd-catalyzed carbonylation

Syntheses of (+)-goniopypyrone and (+)-goniotriol isolated from Goniothalamus giganteus were achieved. The key steps involve Pd-catalyzed carbonylation for lactone ring formation and diastereoselective reduction of ynone using the (R)-CBS catalyst and borane dimethyl sulfide complex.     

Stereoselective synthesis of (+)-isoindolo-β-carboline

Starting from homophthalic anhydride and (S)-tryptophan, the stereoselective synthesis of (+)-isoindolo-β-carboline has been described via the corresponding homophthalimide, its chemoselective oxidative ring contraction, and the intramolecular dehydrative ring closure followed by a geometry-specific demethoxycarbonylation.     

Enantioselective total synthesis of cis-(+)- and trans-(+)-disparlure

An expedient enantioselective synthetic approach for the gypsy moth sex-attractant pheromone cis-(+)-1 and trans-(+)-disparlure 2 is described employing the optimized combination of organocatalytic MacMillan’s self aldol reaction, Wittig olefination, regioselective ring opening of an epoxide and Mitsunobu esterification reactions as key steps.     

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.     

Stereoselective total synthesis of (+)-boronolide, (+)-anamarine, 8-epi-spicegerolide

A stereoselective total synthesis of the naturally occurring cytotoxic lactones (+)-boronolide, (+)-anamarine, and 8-epi-spicigerolide is described. d-Xylose has been used as a chiral source to construct the four contiguous oxygenated stereogenic centers of target molecules. The diastereoselective allylation was performed using Brown’s protocol and the lactone moiety was prepared by ring closing metathesis.     

(+)-Sorangicin A: evolution of a viable synthetic strategy

An effective, asymmetric total synthesis of the antibiotic (+)-sorangicin A (1) has been achieved. Central to this venture was the development of first- and second-generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a Co₂(CO)₆-alkyne complex, the second involving a KHMDS-promoted epoxide ring formation/opening cascade. Additional highlights include effective construction of the dihydro- and tetrahydropyran ring systems, respectively, via a stereoselective conjugate addition/α-oxygenation protocol and a thioketalization/hydrostannane reduction sequence. Late-stage achievements entailed two Julia-Kociénski olefinations to unite three advanced fragments with high E-stereoselectivity, followed by a modified Stille protocol to introduce the Z,Z,E trienoate moiety, thereby completing the carbon skeleton. Mukaiyama macrolactonization, followed by carefully orchestrated Lewis and protic acid-promoted deprotections that suppressed isomerization and/or destruction of the sensitive (Z,Z,E)-trienoate linkage completed the first, and to date only, total synthesis of (+)-sorangicin A (1).     

A new, enantioselective synthesis of (+)-isolaurepan

A highly enantioselective synthesis of 2,6-syn-disubstituted tetrahydropyrans from commercially available tri-O-acetyl-d-glucal, based on a thermal Claisen rearrangement, allows enantioselective synthesis of (+)-isolaurepan when combined with a ring expansion reaction using trimethylsilyldiazomethane.     

Total synthesis of (+)-anamarine

An enantiospecific total synthesis of polyhydroxy δ-pyrone natural product (+)-anamarine is accomplished. The main features of the synthesis include the stereoselective reduction of the ketone obtained by the desymmetrization of the bis-dimethyl amide of tartaric acid and further elaboration involving asymmetric Brown's allylation and ring closing metathesis.     

Total synthesis of (+)-blastmycinone and formal synthesis of (+)-antimycin A3b

The formal synthesis of (+)-antimycin A_3b and the total synthesis of (+)-blastmycinone were achieved using, as a key step, a method developed by us for the synthesis of 2-methyl-1,3-diols via Ti(III)-mediated diastereo- and regioselective opening of trisubstituted 2,3-epoxy alcohols, to carry out the stereoselective construction of the hydroxy-acid segment. An interesting intramolecular radical translocation took place during the epoxide opening process transforming its vicinal PMB-ether in situ, into an ‘1,2-O-(p-methoxy)benzylidene’ ring.     

An asymmetric route to total synthesis of the furano lignan (+)-veraguensin

Total synthesis of the furano lignan (+)-veraguensin is described. The key steps involve a diastereoselective aldol-type condensation of an ester enolate having an α-chiral center with an aromatic aldehyde and a novel isomerization of the syn vicinal substituents on the furan ring via a ring opening-ring closing protocol.     

A highly diastereoselective oxa-Pictet-Spengler approach to (+)-astropaquinone B and (+)-astropaquinone C and the formation of astropaquinone B dimer

A concise and highly diastereoselective synthesis of (+)-astropaquinone B and (+)-astropaquinone C is reported. The synthetic strategy is based on an efficient combination of Dötz benzannulation using a chiral alkyne to construct the naphthalene unit and a highly diastereoselective oxa-Pictet-Spengler reaction to install the trans-configured pyran ring as the key steps.     

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.     

Stereoselective synthesis of (+)-IKD-8344

Total synthesis of IKD-8344 was accomplished via stepwise cyclodimerization of the monomeric seco acid under Yamaguchi conditions. In the synthesis of the monomeric seco acid, Wittig olefination reaction was employed for an efficient bond formation at C7-C8. The threo-trans oxolane unit for the rings a and c was prepared via intramolecular Williamson ether synthesis of the hydroxyl mesylate prepared via asymmetric aldol reaction. Radical cyclization of a β-alkoxymethacrylate intermediate furnished the threo-cis oxolane unit for the b ring fragment.     

Enantiopure N-Boc piperidine-2-ethanol for the synthesis of (+)- and (−)-dumetorine,and (+)- and (−)-epidihydropinidine

The convenient synthesis of both enantiomers of the piperidine alkaloids such as dumetorine and epidihydropinidine is described. Pure enantiomers of 2-(2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester are used as a common starting material. The syntheses are based on a RCM reaction and on methylation of the piperidine ring according to Beak–Lee methodology, respectively.     

Enantioselective Total Synthesis of (+)-Nordasycarpidone, (+)-Dasycarpidone,and (+)-Uleine

The structure of uleine type alkaloids is characterized by the presence of a bridged tetracyclic hexahydro-1H-1,5-methanoazocino[4,3-b]indole ring system 1 . Various strategies have been developed to access this polycyclic structural motif. We report herein a one-step conversion of appropriately functionalized 1,3,4-trisubstituted cyclopent-1-ene to 1 by way of an integrated oxidation/reduction/cyclization (iORC) process. This domino sequence, initiated by oxidative cleavage of cyclopentene ring, generated subsequently a cyclohexenone, an indole and a 1,3-bridged piperidine ring through formation of one C−C and two C−N bonds. Compound 1 is subsequently converted to nordasycarpidone, dasycarpidone and uleine. The chirality of the molecule was introduced by enzymatic desymmetrization of commercially available meso cis-3,5-diacetoxy-1-cyclopentene.     

Total synthesis of akuammiline alkaloid (+)-strictamine

An asymmetric total synthesis of the akuammiline alkaloid (+)-strictamine is described. The key steps of the synthetic route involve an improved Johnson-Claisen rearrangement to facilitate the formation of the challenging C15–C20 linkage and the (E)-alkene side chain, intramolecular nucleophilic substitution cyclization to establish the E ring and diastereoselective Brown hydroboration of the terminal alkene to introduce the C16 stereocenter.     

An efficient synthesis of (+)-decursinol from umbelliferone

An efficient, practical and enantioselective total synthesis of (+)-decursinol, which has diverse range of biological properties including anti-cancer, anti-Helicobacter pylori, and strong antinociceptive activities, has been achieved in five steps with 41.4% overall yield from umbelliferone. The improved ring construction from coumarin to linear pyranocoumarin has been obtained through quinonemethide intermediate by using phenylboronic acid with propionic acid.     

A fully stereocontrolled total synthesis of (+)-leucascandrolide A

A highly stereocontrolled total synthesis of leucascandrolide A, a cytotoxic 18-membered macrolide from the calcareous sponge Leucascandra caveolata, starts out with a Jacobsen asymmetric hetero Diels-Alder reaction to configure the 2,6-cis-tetrahydropyran ring. All the remaining oxygenated stereocentres are introduced with high selectivity by relying on substrate-based control. An efficient endgame depends on two Mitsunobu reactions, the first to close the macrolactone with inversion at C17 and the second to attach the oxazole-containing side chain at C5, followed by Lindlar hydrogenation of the two alkynes to provide (+)-leucascandrolide A.     

A concise sequential photochemical-metathesis approach for the synthesis of (+)-castanospermine and possible uniflorine-A stereoisomers

A recently developed strategy for polyhydroxylated indolizidine ring construction has been applied to the synthesis of (+)-castanospermine and possible isomers of uniflorine-A. The routes to these targets rely on the use of the earlier discovered photocyclization reaction of pyridinium perchlorate in a concise route for preparation of a key N-allylacetamidocyclopentendiol intermediate. Ring rearrangement metathesis of this substance gives an allyl-tetrahydropyridine, which is then transformed to the targets by execution of regio- and stereo-controlled hydroxylation processes followed by indolizidine ring construction.     

Total syntheses of the sesquiterpenoids (+)-trans-dracunculifoliol and (+)-4-hydroxyoppositan-7-one

Sesquiterpenoids (+)-trans-dracuncuflifoliol (1) and (+)-4-hydroxyoppositan-7-one (2) were prepared stereoselectively from enantiomerically pure (7aR)-7a-methyl-1,2,5,6,7,7a-hexahydro-4H-inden-4-one ((−)-6), whose synthesis was described herein. Conjugate addition of the organocopper (I) reagent 10 to (−)-6, followed by epimerization of the ring junction, generated 3 of the 4 contiguous chiral centers of both natural products.