A stereoselective synthesis of the hexahydroazepine core of (−)-balanol

A stereoselective synthesis of the hexahydroazepine core of (−)-balanol is described. The key step of the route includes the bromosulfonamidation of an olefin using the intramolecular sulfilimine group as the nucleophile and the Pummerer ene reaction.     

Stereoselective formal synthesis of (−)-centrolobine

Stereoselective formal synthesis of (−)-centrolobine was achieved from naturally occurring l-(+)-tartaric acid, employing a facile FeCl₃ mediated stereoselective formation of a tetrahydropyran as the key step.     

Formal total synthesis of (−)-balanol: a potent PKC inhibitor

An efficient formal total synthesis of the PKC inhibitor balanol 1 is described, starting from the commercially available pentane1,5-diol. A Shi epoxidation and Pd(0)-mediated nitrogen substitution with double inversion established the correct configuration of the balanol precursor 3.     

A five-step formal synthesis of (−)-Jaspine B

A new application of the sequential hydrolysis-oxidation-Wittig olefination (SHOWO) protocol to a d-glucose derivative, and an anomeric deoxygenation reaction of a xylo-d-furanose derivative is presented for the five-step formal synthesis of (−)-Jaspine B.     

Enantioselective formal total synthesis of (−)-trachyspic acid

An enantioselective formal total synthesis of (−)-trachyspic acid was carried out using, as key steps, an asymmetric aldol reaction of a chiral oxazolidinone and a diastereoselective alkylation of a chiral 1,3-dioxolan-2-one. The key lactone 3 was synthesized in five steps starting from dioxolanone 9.     

Stereoselective formal total synthesis of the cyclodepsipeptide (−)-spongidepsin

The formal total synthesis of (−)-spongidepsin is achieved starting from easily available raw materials involving asymmetric α-hydroxylation, Enders alkylation, and RCM as key reactions.     

Chemoenzymatic formal synthesis of (-)- and (+)-epibatidine

The cis-dihydrocatechol, derived from enzymatic cis-dihydroxylation of bromobenzene using the microorganism Pseudomonas putida UV4, was converted into (-)-epibatidine in eleven steps with complete stereocontrol. In addition, an unprecedented palladium-catalysed disproportionation reaction gave the (+)-enantiomer of an advanced key intermediate employed in a previous synthesis of epibatidine.     

A formal synthesis of (−)-swainsonine from a chiral aziridine

A formal synthesis of enantiomerically pure (−)-swainsonine was successfully achieved using intramolecular cyclization of the amino alcohol 4 which was derived from a readily available 1-(R)-α-methylbenzylaziridine-2-carboxylic acid (−)-menthol ester 6.     

Chemoenzymatic total synthesis of potent HIV RNase H inhibitor (−)-1,3,4,5-tetragalloylapiitol

Starting from racemic dimethyl 2-acetoxy-3-methylenesuccinate, the chemoenzymatic facile total synthesis of (−)-1,3,4,5-tetragalloylapiitol has been demonstrated via an efficient lipase catalyzed resolution followed by a DIBAL reduction-double gallyolation, osmium tetroxide dihydroxylation-double gallyolation, and reductive global O-benzyl deprotection pathway.     

Efficient synthesis of the key intermediate triptophenolide methyl ether for the synthesis of (−)-triptolide

An efficient synthesis of triptophenolide methyl ether 4 from the readily available abietic acid 3 in nine steps is described and successfully applied to the synthesis of (−)-triptolide 1. The route is of characteristic of low cost, high yield and easy operation. In addition, every reaction in this route has been successfully scaled-up to a 100 g substrate level without loss of yield.     

A common approach to pyrrolizidine and indolizidine alkaloids; formal synthesis of (−)-isoretronecanol, (−)-trachelanthamidine and an approach to the synthesis of (−)-5-epitashiromine and (−)-tashiromine

A common and short stereoselective route is described for the formal synthesis of pyrrolizidine alkaloids, (−)-isoretronecanol and (−)-trachelanthamidine. An approach to the synthesis of indolizidine alkaloids (−)-5-epitashiromine and (−)-tashiromine utilizing ring closing metathesis is also described starting from commercially available and inexpensive l-proline.     

Asymmetric formal synthesis of (−)-pancracine via catalytic enantioselective C-H amination process

The reaction of silyl enol ethers derived from cyclohexanone with [(4-nitrophenylsulfonyl)imino]phenyliodinane (pNsNIPh) catalyzed by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh₂(S-TCPTTL)₄, provides, after desilylation, N-pNs-protected (S)-β-aminocyclohexanone in up to 72% ee. This represents the first example of the insertion of nitrene species into an allylic C-H bond of silyl enol ethers. Using this process, a new catalytic asymmetric route to an advanced intermediate in Overman's synthesis of the montanine-type Amaryllidaceae alkaloid (−)-pancracine has been developed. The key steps involve (a) a one-pot Rh₂(R-TCPTTL)₄-catalyzed sequential 1,4-hydrosilylation/enantioselective C-H amination of 2-cyclohexen-1-one, (b) N-alkylation and subsequent intramolecular Mukaiyama aldol reaction/dehydration, and (c) a regio- and stereocontrolled reductive deoxygenation of bicyclic enone 27 with migration of the double bond to create the C1/C11a double bond and the stereogenic center at C11 of 3-arylhexahydroindole 31.     

Synthesis of indole alkaloid (−)-corynantheidol and formal synthesis of (−)-corynantheidine via one-pot asymmetric azaelectrocyclization

The highly efficient asymmetric total synthesis of indole alkaloid, (−)-corynantheidol, containing a 2,4,5-trisubstituted piperidine core, was achieved using a new version of the one-pot azaelectrocyclization reaction. The formal synthesis of (−)-corynantheidine was also achieved using the common synthetic intermediate for these corynantheines.     

Enantioselective syntheses of 3,4,5-trisubstituted γ-lactones: formal synthesis of (−)-blastmycinolactol

A kinetic resolution process of Rh-catalyzed intramolecular Alder-ene reaction is described along with the studies of the substrate scope and stereochemistry of this remarkably efficient process. 3,4,5-Trisubstituted γ-lactones were synthesized in high enantioselectivity (>99% ee) and efficiency. The formal asymmetric syntheses of (−)-blastmycinolactol and (+)-blastmycinone, degradation products of the macrocyclic dilactone (+)-antimycin, were reported to address the applications of this methodology.     

Radical cyclizations of acylsilanes in the synthesis of (+)-swainsonine and formal synthesis of (−)-epiquinamide

Radical cyclization of acylsilane is an useful synthetic methodology. To demonstrate the versatility of this method using the cyclization as a key step, polyhydroxylated indolizidine (+)-swainsonine was synthesized through two different bond connection approaches to construct the bicyclic skeleton. In the first approach, we used 2,3-isopropylidene-d-ribono-1,4-lactone (20) as a chiral building block to form the indolizidine skeleton through a 1,6-cyclization. In the second approach, (S)-(+)-5-oxo-2-tetrahydrofurancarboxylic acid (23) was used to construct the same ring system through a 1,5-cyclization. Starting from acid 23, we also synthesized exo-1-hydroxyquinolizidin-4-one (56), which was a synthetic intermediate in the synthesis of polyhydroxylated quinolizidine (−)-epiquinamide.     

Chemoenzymatic enantiodivergent total syntheses of (+)- and (−)-codeine

Whole-cell fermentation of β-bromoethylbenzene with the recombinant strain Escherichia coli JM109 (pDTG601) that over-expresses toluene dioxygenase provided the corresponding cis-dihydrodiol 19, which served as a starting material for both enantiomers of codeine. The key intermediate for the synthesis of (+)-codeine was diol 25b, whose Mitsunobu coupling with bromoisovanillin was followed by an intramolecular Heck cyclization to aldehyde 35b. Elaboration of this material to vinyl bromide 27b allowed for the second Heck cyclization 36b. Adjustment of the C-6 stereogenic center and hydroamination completed the synthesis of ent-codeine in 14 steps from β-bromoethylbenzene. Diol 33b was converted via Mitsunobu reaction to epoxide 29, whose allylic opening with bromoisovanillin provided ether 54, the enantiomer of 35b. The synthesis of (−)-codeine was completed via two Heck cyclizations and a hydroamination protocol, in an analogous manner as that of ent-codeine. In addition, both enantiomers of epoxide 29, convenient precursors for the coupling with bromoisovanillin, were prepared from diol 33b by Mitsunobu reactions and cyclizations of the trans-diol moiety. Spectral and experimental data are provided for all compounds.     

Racemic synthesis of an intermediate for the formal synthesis of madindoline A and B

On the basis of the application of the Darzens/ring-expansion process of cyclobutenedione developed previously by our group, a new strategy for the multisubstituted cyclopentene units of madindoline A and madindoline B has been reported in this paper. In light of the strategy, the synthesis of racemic Omura’s intermediate was finished in four steps and 34% overall yield, which furnished a new formal synthetic route to madindolines A and B.     

Chelation-controlled reduction: an enantioselective synthesis of (−)-tarchonanthuslactone

The total synthesis of tarchonanthuslactone (1) has been achieved by two different routes. In the first approach, LiAlH₄-LiI reduction and RCM protocols, and in the second approach, Wacker oxidation and LiAlH₄-LiI reduction were used as key steps.     

Stereoselective synthesis of (−)-jimenezin

Total synthesis of jimenezin was achieved via radical cyclization of β-alkoxyacrylate and β-alkoxyvinyl sulfoxide intermediates and intramolecular olefin metathesis reaction.     

Asymmetric synthesis of (−)-tetrahydrolipstatin

Attempts toward the asymmetric synthesis of (−)-tetrahydrolipstatin are described. A palladium catalyzed Wacker-type reaction to convert an alkene to a ketone, highly diastereoselective reduction of a β-hydroxy ketone, selective oxidation of a diol, and modular synthesis are the key features of the successful approach.