The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″

The enantioselective synthesis of indolizidines (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″ has been achieved and the absolute stereochemistry of both indolizidines 203A and 233D was established as 5S,8R,9S. The relative stereochemistry of natural 231C was established by the present asymmetric synthesis.     

Total synthesis of (−)-physovenine from (−)-3a-hydroxyfuroindoline

Total synthesis of calabar bean alkaloid (−)-physovenine (−)-3 has been achieved in a concise manner starting from optically active (−)-3a-hydroxyfuroindoline (−)-2, synthesized via modified Sharpless epoxidation of tryptophol 1. Our strategy involved a stereospecific radical substitution reaction and regioselective oxidation at the C5 position.     

Synthesis of the fungal natural product (−)-xylariamide A

The first synthesis of the fungal natural product (−)-xylariamide A 1 is reported. N,O-Bis(trimethylsilyl)acetamide induced coupling of d-tyrosine with (E)-but-2-enedioic acid 2,5-dioxo-pyrrolidin-1-yl ester methyl ester 5 produced the dechloro natural product 6, which was subsequently monochlorinated using oxone and KCl to yield synthetic 1. (−)-Xylariamide A 1, (+)-xylariamide A 2 and (−)-dechloroxylariamide A 6 displayed no cytotoxic or antimicrobial activity.     

Formal total synthesis of (−)-spongidepsin

The formal total synthesis of (−)-spongidepsin is described. Three fragments I, II, and III were first prepared from readily available starting materials and then assembled to the target compound. The key steps involved in the synthesis are asymmetric α-hydroxylation, Ender's alkylation, and ring-closing metathesis reactions. An alternative route for the fragment II is also achieved involving Sharpless asymmetric epoxidation and Gilman's alkylation as key reactions.     

Synthesis of the marine furanoditerpene (−)-marginatone

A synthesis of the marine labdane furanoditerpene (−)-marginatone 1 has been accomplished by a short sequence of reactions starting from (+)-coronarin E 5. The key step is the stereocontrolled-intramolecular electrophilic cyclisation of the (+)-dihydrocoronarin E 6, to the tetracyclic marginatane skeleton 7, which is subsequently functionalized by allylic oxidation to give 1. As (+)-coronarin E 5 was previously synthesized from (−)-sclareol 10, the herein reported preparation constitutes the first formal total synthesis of (−)-marginatone 1, by which its absolute configuration has been confirmed.     

Stereoselective total syntheses of (+)-exo- and (−)-exo-brevicomins, (+)-endo- and (−)-endo-brevicomins, (+)- and (−)-cardiobutanolides, (+)-goniofufurone

Stereoselective total syntheses of aggregation pheromones (+)-exo-brevicomin (9a), (−)-exo-brevicomin (9b), (+)-endo-brevicomin (9c), (−)-endo-brevicomin (9d) and styryllactones (+)-cardiobutanolide (14a), (−)-cardiobutanolide (14b), and (+)-goniofufurone (19a) were achieved in good yields from enantiomerically pure highly functionalized furanoid glycal building blocks (1a-d) involving similar synthetic strategies, thus making these furanoid glycals highly useful building blocks in diversity-oriented synthesis (DOS).     

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.     

Gold catalysis in stereoselective natural product synthesis: (+)-linalool oxide, (−)-isocyclocapitelline, and (−)-isochrysotricine

A stereoselective synthesis of the tetrahydrofuran-containing natural products (2S,5R)-(+)-linalool oxide (1), (−)-isocyclocapitelline (2), and (−)-isochrysotricine (3) is reported. Key steps are the copper-mediated S_N2′-substitution of propargyl oxiranes 7 and the gold-catalyzed cycloisomerization of dihydroxyallenes 8/17, resulting in a highly efficient center-to-axis-to-center chirality transfer. The enantioselective total synthesis of (−)-isocyclocapitelline (2) and (−)-isochrysotricine (3) allowed the elucidation of the absolute configuration of these β-carboline natural products.     

Total synthesis of (−)-amathaspiramide F

The stereoselective total synthesis of the marine alkaloid, (−)-amathaspiramide F (1), was achieved from the α-hydroxy-α-ethynylsilane 2. The key steps involved in the synthesis were (1) the enolate Claisen rearrangement of the α-acyloxy-α-alkenylsilane for the stereoselective construction of the consecutive C5 and C9 chiral centers of 1 (erythro configuration), (2) the construction of aza-spirohemiaminal 28, and (3) dibromination during the final stage of the total synthesis. The reaction of the (Z)-α-acyloxy-α-alkenylsilane 22 possessing the Boc-homoallylglycine ester as the acyloxy group underwent stereoselective enolate Claisen rearrangement to give the desired erythro product 23. On the other hand, the reaction of the α-acyloxy-α-alkenylsilane (Z)-5 having Boc-proline gave the unexpected threo product 6. Oxidative cleavage of the vinylsilane group of 23 followed by treatment with heptamethyldisilazane as the methylamine equivalent gave aza-spirohemiaminal 28. The problematic regioselective dibromination to 28 was achieved using n-Bu₄NBrCl₂.     

Stereoselective synthesis of (−)-allosedamine

A stereoselective synthesis of (−)-allosedamine is disclosed. β-Aminosulfoxide 4 was generated stereoselectively by condensation of the sulfinyl anion 2 with N-Ts imine 3. The bromohydrin 5 was obtained by intramolecular sulfinyl group participation and the piperidine ring of allosedamine was elaborated using the ring-closing metathesis (RCM) reaction.     

Flexible approach for the asymmetric synthesis of (−)-hyacinthacine A1 and its 7a-epimer

The diastereoselective nucleophilic addition of organic boronic ester to 3-hydroxy-2-substituted N-acyliminium ions 9 led to the formation of 2,5-cis-pyrrolidine 10, from which a convenient synthesis of (−)-7a-epi-1 was developed. In addition, an efficient asymmetric synthesis of (−)-hyacinthacine A1 1 was achieved through the reduction/ring-opening process.     

Synthesis of (−)-lapatin B

The synthesis of (−)-lapatin B (1) has been achieved from l-tryptophan. The key reactions involve oxidative cyclization of N,N-diacetylglyantrypine (8) using PhI(OH)(OTs), and an indole-to-oxindole transformation in the penultimate step.     

A versatile synthesis of (+)-deoxoprosopinine and (−)-deoxoprosophylline

An efficient synthesis of (+)-deoxoprosopinine and (−)-deoxoprosophylline was achieved from N-benzyl-N-Boc serine derivatives (7) and (7′).     

New synthesis of (−)- and (+)-actinobolin from d-glucose

The total synthesis of (−)-actinobolin 2, an antipode of the natural product starting from d-glucose is described. A three-component coupling reaction of a functionalized cyclohexenone (+)-6, derived from d-glucose by way of Ferrier's carbocyclization, with vinyl cuprate and an aldehyde (R)-5 effectively constructed the carbon framework of 2 in a highly stereoselective manner. The formal synthesis of the natural enantiomer 1 from d-glucose was also achieved.     

First total synthesis and absolute configuration of naturally occurring (−)-hyacinthacine A7 and its (−)-1-epi-isomer

A convergent synthesis of the naturally occurring alkaloid (−)-hyacinthacine A₇, a glycosidase inhibitor of the pyrrolizidine class, is described. The homochiral starting material was tri-orthogonally protected DMDP 10, derived from d-fructose. Key steps of the synthesis were the carbon-chain lengthening at C(5′) in 10 to the α,β-unsaturated pyrrolidine ketone 12 and the one-pot construction of the bicyclic pyrrolizidine system of 13 and 14. Another key step was the partial inversion of the configuration at C(1) in 13 which led, after total deprotection, not only to the naturally occurring target molecule 9 but also to its (−)-1-epi-isomer 19.     

A short synthesis of (+) and (−)-falcarinol

A short, practical synthesis of the bis-acetylenic natural product falcarinol 1 is reported. This method relies on the alternate functionalisation of bis-trimethylsilylbutadiyne 10. This may be achieved in one-pot, however, better yields were obtained more conventionally. Lipase mediated enzymatic kinetic resolution of the racemic adduct in an organic solvent afforded (+)-1 in 97% enantiomeric excess. The analogous process performed with racemic 3-acetoxy falcarinol 11 under aqueous conditions gave (−)-1. Oxidation of 1 with Dess-Martin periodinane gave falcarinone 2.     

Second-generation total synthesis of (−)-diversifolin

A second-generation total synthesis of (−)-diversifolin has been achieved by a more straightforward strategy, involving a highly stereochemistry-dependent 10-membered ring-closing metathesis and a stereoselective dihydroxylation/lactone transposition sequence. Compared to our previous synthesis, the present synthesis is improved in the yield of the key intermediate 2 (20% in 12 steps from diol 8).     

A practical synthesis of (−)-kazusamycin A (revised)

We describe herein a stereo-controlled and practical synthesis of three key building blocks, namely Segment AB′, Segment D, and Segment E′ needed for the total synthesis of (−)-kazusamycin A.     

A facile synthesis of 1,4-dideoxy-1,4-imino-l-ribitol (LRB) and (−)-8a-epi-swainsonine from d-glutamic acid

A facile synthesis of (−)-8a-epi-swainsonine 2 and 1,4-dideoxy-1,4-imino-l-ribitol (LRB) 4 has been achieved by using the versatile building block 3, which was available from cheap d-glutamic acid. The new forming stereogenic center in synthesis of 2 was constructed by highly selective reduction of the ketone 13 with Li(t-BuO)₃AlH in THF (dr=95:5).     

A new synthesis of (−)-thioambrox and its 8-epimer

This new and straightforward synthesis of (−)-thioambrox 2, a sulphur compound whose odour resembles ambergris, starts from sclareolide 4. The stereoselectivity of the final cyclization is independent of the catalyst selected, and compound 2 is always favoured over (+)-iso-thioambrox 3. With hydrochloric acid as catalyst, the cyclization is unexpectedly stereospecific to give 2 in high yield at room temperature.