An expeditious formal synthesis of (−)-epibatidine

A short route to (−)-epibatidine is described. It includes a hetero-Diels–Alder reaction of a chiral non-racemic acyl-nitroso derivative and 2-t-butyldimethylsilyloxycyclohexadiene followed by chemical manipulations to furnish a known precursor of the natural product in 11% overall yield.     

Asymmetric total synthesis of (+)-isocryptotanshinone and formal synthesis of (−)-cryptotanshinone

The first asymmetric total synthesis of (+)-isocryptotanshinone was achieved in 12 linear steps with 12% overall yield from commercially available dihydrobenzopyrone. The key step was a base-mediated cyclization reaction. In addition, the synthetic strategy included the formal synthesis of (−)-cryptotanshinone.     

Stereoselective synthesis of (−)-synargentolide B

A convergent, enantioselective total synthesis of (?)-synargentolide-B has been accomplished from readily available l-arabinose and d-ethyl lactate by a 10-step sequence involving Still-Gennari olefination, one-pot acidic deprotection/lactonization and olefin cross-metathesis reaction as the key step.     

A total synthesis of polyether antibiotic (−)-A23187 (calcimycin)

A total synthesis of (−)-A23187 (calcimycin) was accomplished by a convergent approach. The key step of synthesis was the stereospecific cyclization of the β-hydroxy ketone into the spiroketal under basic conditions.     

A novel synthesis of (−)-callicarpenal

Callicarpenal, isolated from the leaves of American beautyberry (Callicarpa americana) and Japanese beautyberry (Callicarpa japonica), exhibits significant mosquito bite-deterring activity and repellent activity against ticks and fire ants. The mosquito bite-deterring activity level of callicarpenal was reported to be similar to that of N,N-diethyl-m-toluamide. The novel synthesis of (?)-callicarpenal reported herein was accomplished by starting from (+)-pulegone. In our original approach, a novel Prins-type cyclization based on Meyer–Schuster rearrangement was featured as a key step.     

Total synthesis of (−)-seimatopolide A

The total synthesis of (?)-seimatopolide A is described in a linear fashion with high yielding steps. The key reactions include Lu’s isomerization, Sharpless asymmetric dihydroxylation and Kita’s macrolactonization.     

Total synthesis of (−)-phaeosphaeride B by a biomimetic conversion from (−)-phaeosphaeride A

We have accomplished the first total synthesis of STAT3 inhibitory (?)-phaeosphaeride A and its stereoisomer (?)-phaeosphaeride B. This work confirms the configurational assignment of these natural products. Notably, TFA-mediated dehydrative stereoinversion of phaeosphaeride A afforded phaeosphaeride B, based on our hypothesis of the biosynthesis mechanism of phaeosphaeride B from phaeosphaeride A.     

First total synthesis of (−)-aplyolide A

The first total synthesis of (−)-aplyolide A², (16S)-methyloxacyclohexadeca-(5Z,8Z,11Z,14Z)-tetraen-2-one, 1 is reported. The synthesis is based on three consecutive couplings of terminal alkynes with propargylic halides and proves the absolute configuration of the stereogenic center of the natural product.     

Asymmetric synthesis via aziridinium ions: exploring the stereospecificity of the ring opening of aziridinium ions and a formal synthesis of (−)-swainsonine

The use of aziridinium ions in two different projects is described. First, the stereospecificity of the ring opening of aziridinium ions with MeNH₂ as a route to chiral diamines has been explored. When the aziridinium ion contained a phenyl or para-methoxyphenyl substituent, stereospecific ring opening occurred. In contrast, switching the para-methoxy group to a para-N,N-dimethylamino group gave a racemic diamine product. Second, starting from N-Boc pyrrolidine, asymmetric lithiation-trapping-ring expansion (via an aziridinium ion) was used to synthesise a piperidine alcohol. In this way, a formal synthesis of (?)-swainsonine was completed.     

Total synthesis of (−)-cleistenolide and formal synthesis of herbarumin I via a diastereoselective modulable allylation

A modulable tin based allylation method for the synthesis of 1,2,3-triols is described. The optimization of the reaction was aided by ¹H and ¹¹⁹Sn low temperature NMR spectroscopic investigations, which support the formation of two cyclic intermediates after transmetallation. Depending on the nature of the Lewis acid, either syn/anti or anti/syn configured triols could be obtained with good stereocontrol. To demonstrate the value of this methodology and the resulting scaffolds, they were used to install the signature triol motifs of (?)-cleistenolide and of herbarumin I.     

Studies on the synthesis of chiral nonracemic 3,4-disubstituted azepanes,a formal synthesis of (+)- and (−)-balanol

Sugar lactones were converted to 3,4-disubstituted azepanes and caprolactam derivatives by selective deoxygenation, functionalization and reductive cyclization. The cyclization proved troublesome with 6-azidolactols but led to good results with the corresponding lactones. A formal synthesis of (+)- and (−)-balanol is reported.     

Stereoselective total synthesis of (−)-zeylenol,a key intermediate for the synthesis of (+)-pipoxide, (−)-uvarigranol G and (−)-tonkinenin A

Total synthesis of (?)-zeylenol, a key intermediate for the synthesis of (+)-pipoxide, (?)-uvarigranol G and (?)-tonkinenin A was achieved from commercially available starting material d-mannose. The key steps are mixed aldol condensation, Grignard reaction, ring closing metathesis and regioselective benzoylation.     

A general strategy for the formal synthesis of (−)-trans-kumausyne and total synthesis of (5R)-Hagen’s gland lactones from diacetone-d-glucose

A general strategy for the formal synthesis of (−)-trans-kumausyne 1 via the bicyclic lactone (3aR,5R,6aR)-4 and total synthesis of (5R)-Hagen’s gland lactones 2 and 3 via bicyclic lactone (3aR,5S,6aR)-5 starting from diacetone-d-glucose 6 is described. Syntheses of 4 and 5 were achieved by Wittig olefination–lactonization–Michael addition of the corresponding lactols 16 and 17, respectively.     

De novo asymmetric synthesis of (−)-nanaomycin A

The de novo asymmetric total synthesis of (?)-nanaomycin A is described. The entirely linear route required only 13 steps from commercially available starting materials (3% overall yield). Key transformations include a Claisen rearrangement, an asymmetric dihydroxylation, a regioselective tosylation, a diastereoselective intramolecular Friedel-Crafts alkylation and a nitrile hydrolysis. As the route relies on a Sharpless asymmetric dihydroxylation it is equally amenable for the synthesis of (+)-nanaomycin A.     

First stereoselective total synthesis of (−)-stagonolide A

The first stereoselective total synthesis of the nonenolide (?)-stagonolide A is described. Olefin metathesis and epoxide opening reaction are the key steps involved.     

Stereoselective allylation of α-hydroxy aldimines and its application to the formal synthesis of (−)-β-conhydrine

Stereoselective allylation of N-p-methoxyphenyl (PMP)-substituted α-hydroxy aldimines is described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The addition of the allyl group generates a new stereocenter and affords the syn vicinal amino alcohol. Formal synthesis of (?)-β-conhydrine (1) was accomplished via syn-selective allyl addition to N-PMP-substituted α-hydroxy aldimine.     

Enantioselective formal synthesis of (−)-ovalicin using quinic acid as a chiral template

The key intermediate 18 for the synthesis of (−)-ovalicin was synthesized using (−)-quinic acid as the chiral source, through a series of stereocontrolled and efficient chemical reactions, thus establishing a new, formal synthesis of the natural target. The featuring spirocyclic epoxide function has been installed by internal Williamson ether synthesis using the functionalities originally present at C-1 of (−)-quinic acid after the appropriate adjustments required to introduce the necessary functionality at C-2.     

A formal total synthesis of (±)-strigol

A novel route to the tricyclic compound (±)-6, a known precursor to (±)-strigol is disclosed.     

A convergent approach for the total synthesis of the α-glucosidase inhibitor (−)-panaxjapyne-C

The stereoselective total synthesis of (?)-panaxjapyne-C was accomplished in a convergent fashion. The synthesis utilizes the readily available enantiomers l-(+)-diethyltartrate and d-(?)-diethyltartrate and involves a Cadiot–Chodkiewicz coupling reaction, and an Ohira–Bestmann reaction as the key steps.     

A convergent approach towards the synthesis of the 2-alkyl-substituted tetrahydroquinoline alkaloid (−)-cuspareine

A convergent approach towards the synthesis of the 2-alkyl-substituted tetrahydroquinoline alkaloid (?)-cuspareine via enantiospecific construction of the (R)-benzyl 2-formyl-3,4-dihydroquinoline-1(2H)-carboxylate. We have achieved an efficient enantiospecific synthesis of (?)-cuspareine starting from known key starting materials. The reactions employed for individual transformations are simple and high yielding, and the strategy could potentially be easily extended.