Asymmetric synthesis of (+)-chloriolide

An asymmetric synthesis of 12-membered ring macrolide, chloriolide has been accomplished by adopting a linear strategy. Lipase-catalyzed enzymatic kinetic resolution (EKR), asymmetric alkynylation using Trost pro-phenol catalyst followed by Yamaguchi macrolactonization has been successfully employed to achieve the target molecule.     

Asymmetric synthesis of (+)-cardiobutanolide

A formal total synthesis of (+)-cardiobutanolide has been accomplished from d-glucose, a readily available precursor.     

Asymmetric synthesis of (+)-abresoline

The first asymmetric synthesis of (+)-abresoline has been achieved starting from the (S)-1-(aryl)homoallylic amine, which was prepared enantioselectively by the method based on allylation of the (R)-2′-(2-naphthyl)-bearing hydroxyoxime ether. This synthetic route employs the TiCl₄-induced intramolecular Mannich-type cyclization of the 1-azadiene-bearing ketal amine as the key steps to afford stereoselectively the cis-2,6-disubstituted piperidine, followed by CBr₄/PPh₃-induced dehydrocyclization for the elaboration of the amino alcohol to the trans-4-arylquinolizidine.     

Asymmetric synthesis of (+)-negamycin

An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity. Conversion of 4 into beta-alkoxy imine 7 and subsequent CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding homoallylamine 8 with good diatereoselectivity, which was readily converted into (+)-negamycin (1) in 25% overall yield over 11 steps.     

Asymmetric synthesis of (+)-tetrahydropseudodistomin

An efficient asymmetric synthesis of (+)-tetrahydropseudodistomin is described. The important synthetic features include a Maruoka asymmetric allylation and a Sharpless asymmetric dihydroxylation as key steps for the generation of chirality at C-2, -4, and -5 of the trisubstituted piperidine ring.     

Asymmetric synthesis of (+)-vertine and (+)-lythrine

The total syntheses of the Lythracea alkaloids (+)-vertine and (+)-lythrine are described. Enantioenriched pelletierine is used as a chiral building block and engaged into a two step pelletierine condensation leading to two quinolizidin-2-one diastereomers in a 8 : 1 ratio. The major product is used in the synthesis of (+)-vertine via aryl-aryl coupling and ring closing metathesis to provide a Z-alkene α to the lactone carbonyl function. The same procedure was used for (+)-lythrine after base induced epimerization of the main quinolizidin-2-one diastereomer. Alternative classical ring closure strategies like macrolactonisation or aryl-aryl coupling failed.     

Asymmetric synthesis of (+)-L-733,060

A concise, stereocontrolled synthesis of (+)-L-733,060 was achieved. Key features involve diastereoselective oxazoline formation catalyzed by palladium(0) and intramolecular cyclization by catalytic hydrogenation of an oxazoline.     

Asymmetric total synthesis of (+)-fostriecin

[structure: see text] The title compound, a potent protein phosphatase inhibitor and anticancer agent, was prepared by an efficient, multiconvergent asymmetric synthesis. Key transformations include a ring forming olefin metathesis leading to the alpha,beta-unsaturated lactone and creation of the triene moiety via Suzuki cross-coupling.     

Asymmetric total synthesis of (+)-swainsonine

A concise asymmetric synthesis of (+)-swainsonine (ent-1) is described starting from 2, which was readily prepared from commercially available l-glutamic acid. The method features installation of the indolizidine ring via an intramolecular cyclisation of α-sulfinyl carbanion as a key step. (+)-Swainsonine was obtained in 11.8% overall yield in 10 steps.     

Asymmetric synthesis of (+)-trachyspic acid

Aldol reaction of di-tert-butyl 4-(4-methoxybenzyloxy)-2-oxobutanoate with pent-4-enal using (S)-1-(3,5-bis(trifluoromethyl)phenyl)-3-(pyrrolidin-2-ylmethyl)thiourea hydrochloride as a catalyst, followed by Pinnick oxidation and tert-butyl esterification, gave (2S,3S)-di-tert-butyl 2-(2-(4-methoxybenzyloxy)ethyl)-3-allyl-2-hydroxysuccinate in high optical purity (85% ee), from which the total synthesis of (+)-trachyspic acid, a tumor cell heparanase inhibitor, was accomplished.     

Asymmetric total synthesis of (+)-cannabisativine

The asymmetric total synthesis of natural (+)-cannabisativine 1 was completed in 19 steps and 7% overall yield. The key synthetic intermediate 29 was prepared with a high degree of stereocontrol in 12 steps starting from chiral 1-acylpyridinium salt 10. Addition of zinc enolate 11 to pyridinium salt 10 furnished dihydropyridone 12 containing two contiguous stereocenters of the correct absolute configuration. Luche reduction of ketone 16 afforded diol 17 in high yield (96%) and excellent diastereoselectivity. The Mukaiyama-Michael reaction of pyridones 27a/b with O-silyl ketene acetal 32 gave phenyl selenyl ketones 33a/b with complete stereoselectivity. Elimination of cis-beta-hydroxyselenides 34 and 35 effected the regiocontrolled preparation of tetrahydropyridine derivative 29. Several approaches to the macrocyclic ring closure of the 13-membered ring were investigated, ultimately leading to the completion of an asymmetric synthesis of the target compound with a high degree of stereocontrol.     

Asymmetric total synthesis of (+)-monocerin

A concise asymmetric total synthesis of (+)-monocerin has been accomplished. The cis-fused furobenzopyranone of monocerin was efficiently constructed via a Lewis acid-mediated stereoselective cyclization of 1,2,4-triols intermediate.     

Asymmetric total synthesis of (+)-curcutetraol and (+)-sydonol

The asymmetric total syntheses of (+)-curcutetraol and (+)-sydonol, phenolic bisabolane-type sesquiterpenoids having chiral tertiary alcohol moiety in the o-position of a phenol, were achieved in high enantiomeric excesses (99% ee). The chiral tertiary benzylic alcohol moiety of these compounds was constructed by an asymmetric synthesis using an easily available chiral aminal, (−)-(2R,5S)-2-methoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane. The absolute configurations of both (+)-curcutetraol and (+)-sydonol have been assumed to be S-configuration based on the stereochemical course of the well established asymmetric synthesis used in the syntheses.     

Asymmetric synthesis of (+)-1-deoxynojirimycin and (+)-castanospermine

Asymmetric total syntheses of (+)-1-deoxynojirimycin (1) and (+)-castanospermine (2) are described. Starting from diene 3, the required absolute stereochemistry is introduced by an asymmetric hydroxylation followed by epoxidation. An intramolecular cyclization of amine 17 gives access to the corresponding tetrasubstituted piperidine 18, which is a precursor to compounds 1 and 2. (+)-Deoxynojirimicyn (1) was obtained in 36% yield over 11 steps from diene 3, while (+)-castanospermine (2) was achieved in 13% after 19 steps from the same starting material.     

Asymmetric total synthesis of (+)-danicalipin A

A convergent asymmetric total synthesis of (+)-danicalipin A is accomplished, in which two chlorinated fragments are stereoselectively joined by 1,3-dipolar coupling, leading to the confirmation of the absolute configuration of the natural product.     

Asymmetric synthesis of (+)-mequitazine from quinine

The first asymmetric synthesis of the antihistaminic drug mequitazine is reported. Our approach started from quinine, a Cinchona alkaloid, whose chiral information was exploited for setting up the stereogenic center of (+)-mequitazine.