First total synthesis of paecilodepsipeptide A

The first total synthesis of paecilodepsipeptide A is reported.A convergent,flexible strategy employing peptide chemistry and culminating in macrolactamisation is described.The previously reported structure of compound is confirmed.     

First stereoselective total synthesis of Neocosmosin A: a facile approach

First stereoselective concise synthesis of Neocosmosin A, with in vitro binding affinity for human opioid and cannabinoid receptors, has been reported using readily available starting materials such as methylacetoacetate, cyclohexanone, and homoallyl alcohol involved in the key transformations. There are three fragments involved in the synthesis of target molecule, bearing acid functionality, (R)-pent-4-en-2-ol, and Weinreb amide which are synthesized in four, eight, and three steps, respectively. Then the fragments were coupled in four steps to yield the target molecule in an overall yield of 28.6%.     

First total synthesis of tuberonic acid

A vinyl group as an acetic acid side chain was attached to the optically active monoacetate of 4-cyclopentene-1,3-diol with CH₂CHMgBr, LiCl, and a CuCN catalyst to produce the S_N2-type product, from which the full carbon skeleton of tuberonic acid was constructed through Mitsunobu inversion, Claisen rearrangement, and Wittig reaction. At the last stage, the THP protective group was removed with MgBr₂ in Et₂O. The diastereomeric ratio of tuberonic acid and the trans isomer was 92:8 by ¹H NMR spectroscopy.     

Chemoenzymatic total synthesis of cryptocaryalactone natural products

A new chemoenzymatic route for the preparation of cryptocaryalactones natural products using a kinetic resolution process as the key step is described. Novozyme-435 catalyzed hydrolysis of the prochiral (±)-monoester 7 afforded the precursors of cryptocaryalactones with high enantiomeric excess and excellent yields. The compounds (4S,6S)-7 and (4R,6R)-7 were converted to (+)-(6R,2′S)-cryptocaryalactone (1) and (?)-(6S,2′R)-cryptocaryalactone (2), respectively by employing Wittig-olefination, lactonization and acylation reactions.     

First total synthesis of eudistalbin A

<正>Eudistalbin A was isolated from marine tunicate eudistoma album and possess cytotoxic activity(ED_(50)3.2μg/mL) in vitro against the growth of KB human buccal carinoma cells.The synthetic eudistalbin A showed potent inhibitory activity against the breast carcinoma cell line MDA-231 with an IC_(50) value of 2.1μmol/L using the metabolic assay MTT.All structures of new compounds were confirmed by ~1H NMR,~(13)C NMR,HRMS and optical rotation.     

Stereoselective total synthesis of cochliomycin A

A convergent and stereoselective synthesis of cochliomycin A, a 14-membered resorcyclic acid lactone, based on chiron approach is described. The key reactions involved olefin cross-metathesis and sodium hydride promoted one-pot intramolecular lactonization. l-Arabinose was used as a chiral pool material for the construction of the key fragment.     

First total synthesis of rhuscholide A,glabralide B and denudalide

The first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity, had been accomplished in 14 linear steps with 10.6% overall yield. In this synthesis, base-mediated phenol ortho-alkylation and piperidine promoted aldol condensation were exploited as key steps. The synthesis was flexible and allowed for the convenient preparation of two analogous natural products glabralide B and denudalide.     

First total synthesis of(±)-sepicanin A

<正>A facile approach for the first total synthesis of naturally occurring geranylated flavanoids sepicanin A has been obtained with total yield 16%starting from 2,4,6-trihydroxyacetophenone after four steps.The key step was the protic acids(HCl or p-TsOH)-catalyzed benzopyrone formation in a protic polar solvent by deprotection and cycUzation of chalcone in one step.     

Toward the natural didemnaketal A: total synthesis of the isomer of didemnaketal A

The total synthesis of isomer of didemnaketal A was achieved in 26 steps. The position of esters is switched at C7 and C8 with respect to their proposed position in natural didemnaketal A, which shows potent anti-HIV activity but so far has not been synthesized in the laboratory. Structural analysis of synthetic isomer of didemnaketal A indicates that the esters at C7 and C8 are correctly assigned, suggesting that the problems for the structural reassignment of natural didemnaketal A lie elsewhere.     

An enantioselective total synthesis of pinnaic acid

An enantioselective and convergent total synthesis of marine natural product pinnaic acid has been achieved. Our general synthetic approach is featured with an asymmetric hydrogenation of racemic γ-keto ester 3, a diastereoselective methylation on the α-methylene of the (1R,5R)-lactone 4, and a diastereoselective Michael addition of the tertiary nitro cyclopentane. The central azaspiro[4.5]decane was constructed utilizing reductive cyclization of the δ-nitroketone followed by highly stereoselective reduction of the cyclic imine with NaBH₄. Ultimately, successive use of triethyl-2-phosphonopropionate and Heathcock's phosphorane 18 to elaborate C5 and C13 side chains completed the total synthesis of pinnaic acid.     

Total synthesis of aldehyde-containing Garcinia natural products isomorellin and gaudichaudione A

The natural products, isomorellin and gaudichaudione A, with a 4-oxa-tricyclo[4.3.1.0^3,7] dec-8-en-2-one scaffold were synthesized for the first time using an efficient method. The key improvement of this method was the simultaneous bisalkylation of 5,6-dihydroxyxanthone with the bulky 2-methylbutyne group. This method obviously shortened the synthetic route and enhanced the total yield. Four analogues named forbesione, desoxymorellin, desoxygaudichaudione A, and gambogin containing the same caged structure were prepared using this method.     

First synthesis of (+)-myxothiazol A

First convergent synthesis of (+)-myxothiazol A (1) was achieved based on modified (one-pot) Julia olefination between (3,5R)-dimethoxy-(4R)-methyl 6-oxo-(2E)-hexenamide (2), corresponding to left-side of the final molecule, and E-4-2′-(1S,6-dimethylheptadiene)-(2,4′-bis-thiazole)-4-methybenzothiazole sulfone (4) corresponding to right-side.     

First total synthesis of (±)-trolline

Trolline, a new bioactive alkaloid was isolated in 2004. We reported herein the first total synthesis of (±)-trolline, in two steps and 18.0% overall yield.     

Enantioselective total synthesis of macrosphelides A and E

Enantioselective synthesis of 16-membered trilactone macrolides, macrosphelide A and E from (S)-lactic acid is described. Key features of the synthesis include the utility of a hitherto unexplored β-ketophosphonate derived from lactic acid and Yamaguchi lactonization leading to the title compounds.     

Formal total synthesis of enigmazole A

A stereoselective formal total synthesis of enigmazole A, a marine macrolide isolated from Cinachyrella enigmatica, is described. Lewis acid mediated intramolecular allylation of an α-acetoxy ether, prepared from alcohol and carboxylic acid fragments was carried out to construct the methylene THP ring with high stereoselectivity. The late-stage macrolactonization of the corresponding seco-acid provided a known synthetic intermediate of enigmazole A.     

First total synthesis of tripdiolide

The first total synthesis of tripdiolide 1 from the readily available abietic acid 3 in 22 steps is described and this synthesis furnishes a 5.8% overall yield of 1 with an average yield of 87%.     

First total synthesis of two nematicidal prenylated flavanones

The total synthesis of(±)-8-(3-methylbut-2-enyl)-2-phenyl-2,3-dihydrochromen-4-one and(±)-2-(4-hydroxyphenyl)-8-(3- methylbut-2-enyl)-2,3-dihydrochromen-4-one was first achieved through C-prenylation,protection of phenolic hydroxyl group, aldol condensation,cyclization and deprotection starting from cheap benzaldehyde,4-hydroxybenzaldehyde and 2-hydroxyacetophenone, with total yield of 20 and 16.3%.All structures of new compounds were confirmed by IR,~1H NMR and MS.     

First total synthesis of four natural prenylated flavonoids

A facile approach for the first total synthesis of prenylated flavonoids,(±)-abyssinone-Vl-4-O-methyl ether 1,(±)-abyssinoneIV -4’-O-methyl ether 2,(±)-abyssinone-V-4’-O-methyl ether 3 and(±)-sigmoidin E 4 has been described.The key intermediate 4-hydroxy-3,5-di-(3-methylbut-2-enyl)benzaldehyde 6 was also first synthesized that features regioselective prenylation of 4-hydroxybenzaldehyde and crystallizing with petroleum ether from the reaction mixture by freeze-out effect.