First total synthesis of ocimarin

<正>A facile approach for the first synthesis of ocimarin,naturally occurring coumarins,was developed by employing a cerium(Ⅲ) chloride heptahydrate-catalyzed Pechmann condensation of phenols andβ-keto esters in a solvent-free system as key step,by which ocimarin was achieved by three steps starting from acetylacetic ether and resorcinol with total yield 23.2%.All structures of new compounds were confirmed by IR,~1H NMR and MS.     

First total synthesis of heterocurvistone

The sesquiterpene ketone (±)-heterocurvistone was synthesized in eight steps and 12% overall yield from known methyl R-(+)-3-(4-methyl-3-cyclohexen-1-yl)-3-butenoate, readily available from R-(+)-limonene. The key synthetic step is an oxymercuration-induced cyclization.     

First total synthesis of fumaridine

The first total synthesis of the alkaloid fumaridine 1a is reported. The key step is the assemblage of the arylmethylene isoindolinone 2a (E) by Horner reaction between the phosphorylated isoindolinone 3a and the suitably substituted benzaldehyde 4. N-Lactam deprotection and concomitant E→Z isomerization complete the synthesis of the title compound.     

First total synthesis of murisolin

The first and concise total synthesis of murisolin (1) was accomplished using asymmetric alkynylation and Sonogashira coupling as the key steps. The threo/trans/threo-type THF ring moiety was constructed with excellent stereoselectivity by asymmetric alkynylation of 1,6-heptadiyne to alpha-tetrahydrofuranic aldehyde, which was also prepared via the asymmetric alkynylation.     

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 achaetolide

The first total synthesis of achaetolide, a 10-membered macrolactone was achieved using Mitsunobu reaction and Grubbs ring-closing metathesis reaction as the key steps for ring construction. The desired stereo centres were generated by Jacobsen hydrolytic kinetic resolution, dihydroxylation and Sharpless asymmetric epoxidation reactions.     

First total synthesis of papilistatin

Papilistatin has been isolated recently and found to have good anticancer and antibacterial activity. Papilistatin is a unique phenanthrene-1,10-dicarboxylic acid. The first total synthesis of papilistatin is described here with radical cyclisation as the key step.     

First total synthesis of mytiloxanthin

The first total synthesis of mytiloxanthin 2 was accomplished via the cyclopentyl ketone 7 prepared by stereoselective rearrangement of the epoxide 4a.     

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.     

First total synthesis of herbarumin III

An asymmetric 10-step total synthesis of herbarumin III in 24% overall yield is described using ring-closing metathesis as the key step.     

First total synthesis of topopyrone C

The first synthesis of topopyrone C, a natural compound and inhibitor of Topoisomerase I, has been carried out by Marschalk alkylation of 1-hydroxy-3,6,8-trimethoxyanthraquinone, followed by a Baker-Venkataraman chain elongation and an acid-catalyzed cyclization for the construction of the pyrone ring.     

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.     

First total synthesis of JS isoprostane

A stereoselective Julia-Lythgoe olefination followed by an efficient 1,3-allylic transposition of the C-9 hydroxyl group of compound 13 has allowed the first total synthesis of J(2) isoprostane (1), a recently discovered member of the growing isoprostane family. This elusive compound opens up numerous new avenues for the molecular biology of cyclopentenone prostaglandins which are endowed of intriguing biological effects such as antitumor, antiinflammatory, and antiviral activities. In principle, our approach is flexible enough to allow an easy synthesis of other isoprostanes of the J family following the same methodology.     

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 asymmetric total synthesis of tetrodotoxin

Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The alpha-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation-reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purified by ion exchange chromatography and characterized to be identical with the natural compound.     

First total synthesis of leucamide A

The first total synthesis of marine bioactive cyclic heptapeptide Leucamide A has been accomplished, including a simple method for construction of the 4,2-bisheterocycle tandem pair substructure that employs a DAST-mediated cyclization of beta-hydroxy amide and final HBTU-promoted ring closing.     

First total synthesis of prunustatin A

In this study, we achieved the first total synthesis of natural prunustatin A (1), a novel inhibitor of glucose-regulated protein 78 (GRP78) expression. A key feature included a 15-membered ring macrocyclization, which was successfully accomplished by employing Shiina macrolactonization using 2-methyl-6-nitrobenzoic anhydride (MNBA) and 4-dimethylaminopyridine (DMAP).     

First stereoselective total synthesis of triumfettamide

The first total synthesis of triumfettamide (1) is described. The asymmetric syntheses of two highly functionalized units—α-hydroxylated C17 monounsaturated fatty acid unit (2) and C26 phytosphingosine (3) have been accomplished involving Sharpless asymmetric dihydroxylation, Sharpless kinetic resolution, regioselective epoxide opening, regioselective DIBAL-H reduction of acetal, Wittig olefination as the key steps. Finally N-acylation of phytosphingosine 3 with (2R,6Z)-2-hydroxy-6-heptadecenoic acid 2 followed by DDQ deprotection of PMB, provided target compound 1.     

First total synthesis of louisianin A

The first total synthesis of louisianin A, 4-allyl-6,7-dihydro-1-hydroxycyclopenta[c]pyridin-5-one, is achieved from 2-chloro-4-cyanopyridine 5 via seven steps in an overall 24% yield. The key step is a cyclization-decarboxylation sequence toward the formation of a cyclopentenone ring.