Total synthesis of mycestericin A and its 14-epimer

The total synthesis of mycestericin A (1) and its 14-epimer 34 is described herein. The Overman rearrangement of an allylic trichloroacetimidate derived from l-tartrate generated a tetra-substituted carbon with nitrogen and subsequent stereoselective transformations afforded the highly functionalized left-half segment, vinyl iodide. Cross-coupling of the vinyl iodide with a chiral organometallic species synthesized from d-tartrate under the Negishi or Suzuki-Miyaura coupling conditions, followed by deprotection, completed the total synthesis of 1. The 14-epimer of mycestericin A was also synthesized, and a comparison of [α]_D values of peracetyl γ-lactone derivatives of mycestericin A and its 14-epimer as well as degradation studies of 1 and 34 fully confirmed the proposed absolute structure of mycestericin A.     

Total synthesis of naturally occurring 5,6,7- and 5,7,8-trioxygenated coumarins

The synthesis of five naturally occurring polyoxygenated coumarins is described. It concerns two 5,6,7-trioxygenated coumarins, i.e., 6-hydroxy-5,7-dimethoxycoumarin (fraxinol) 1 and 5,6,7-trimethoxycoumarin 2, and three 5,7,8-trioxygenated coumarins, i.e., 8-hydroxy-5,7-dimethoxycoumarin (leptodactylone) 3, 5,7,8-trimethoxycoumarin 4 and 8-(3-methyl-2-butenyloxy)-5,7-dimethoxycoumarin (artanin) 5. Key feature of the synthetic pathway is the synthesis of suitable tetraoxygenated benzaldehydes, which are then converted to the corresponding coumarins via a Wittig reaction.     

Total synthesis of lycoperdic acid and its C4-epimer

Efficient stereodivergent syntheses of (+)-lycoperdic acid (LPA) and 4-epi-LPA have been achieved based on asymmetric hydrogenation (H₂, Rh/(R,S)-MeBoPhoz) of racemic enamide as a key step.     

First total synthesis of labeled EPA and DHA-derived A-type cyclopentenone isoprostanoids: [D2]-15-A3t-IsoP and [D2]-17-A4t-NeuroP

A-type cyclopentenone isoprostanoids are abundantly formed in vivo by radical peroxidation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are consumed daily for the prevention of cardiovascular and neurological pathologies. To facilitate in depth studies concerning the effects of these oxidized isoprostanoids on human health, labeled derivatives are necessary. In this paper, we have accomplished the first total synthesis of labeled A-type cyclopentenone isoprostanoids, namely 17,18-[D₂]-15-A_3t-IsoP and 19,20-[D₂]-17-A_4t-NeuroP. The two enantioselective routes are highly convergent, stemming from a common intermediate, readily available by a Julia–Kocienski reaction, and feature the semihydrogenation of an alkyne moiety for the installation of the labeled lower side chain.     

First total synthesis of tenuifolin via PIFA mediated oxidative biaryl coupling

The first total synthesis of a sesquiterpenoid, tenuifolin, was achieved in seven linear steps. Phenyliodine(III) bis(trifluoacetate) (PIFA) mediated oxidative biaryl coupling was employed as a key step to construct the central seven-membered ring with a double bond. The double bond formation was also exploited.     

Total synthesis of (±)-hibiscone C

A total synthesis of (±)-hibiscone C, one member of the furanosteroid family of natural products that also includes viridin and wortmannin, is reported. Two new pathways for formation of the key diacyl furan subunit are described.     

Total synthesis of (-)-5,6,11-trideoxytetrodotoxin and its 4-epimer

[reaction: see text] The first total synthesis of 5,6,11-trideoxytetrodotoxin (1) and its 4-epimer were achieved. The synthesis is characterized by the stereoselective construction of the quaternary amino carbon center at C8a by an asymmetric transferring Strecker synthesis and the highly efficient conversion of cyanohydrin 4 to 1 via intramolecular cyclization reactions.     

Palladium(II)-catalyzed intramolecular aminoacetoxylation of sugar derived alkenyl tosylsulfonamide: Total synthesis of l-deoxyallonojirimycin

Palladium catalyzed intramolecular aminoacetoxylation of d-ribose derived alkenyl tosylsulfonamide to deliver l-deoxyallonojirimycin in an overall yield of 19%. The preliminary screening of l-deoxyallonojirimycin against carbohydrate processing enzymes showed moderate inhibitory activity against α-glucosidase (yeast) and α-mannosidases.     

First total synthesis of Pestalotioprolide C and its C7 epimer

The first total synthesis of Pestalotioprolide C and C7-epi-Pestalotioprolide C adopting Noyori asymmetric reduction, HWE Olefination and Shiina macrolactonization as the key steps has been described.     

Total synthesis of rac-longamide B

rac-Longamide B has been synthesized in six-steps from known starting materials. The synthesis is highlighted by a novel palladium-catalyzed double allylic alkylation of amidopyrroles with 2-butene-1,4-di-tert-butyl dicarbonate.     

Total synthesis of calothrixins A and B via oxidative radical reaction of cyclohexenone with aminophenanthridinedione

Bioactive indolo[3,2-j]phenanthridine alkaloids, calothrixin B and its N-oxide derivative calothrixin A have been synthesized via an oxidative free radical reaction. Calothrixin B is generated from the commercially available 2,4,5-trimethoxybenzaldehyde in only seven steps. The key step in this synthesis is the Mn(OAc)₃ mediated oxidative free radical reaction of 9-(benzylamino)phenanthridine-7,10-dione with cyclohexenone to form 12-benzyl-12H-indolo[3,2-j]phenanthridine-7,13-dione.     

Total synthesis of natural (+)-membrenone C and its 7-epimer

Highly stereoselective asymmetric total syntheses of the polypropionate marine defense substance (+)-membrenone C and its 7-epimer have been achieved. Highlights of the strategy include the utilization of a desymmetrization technique to create five contiguous chiral centres from a single bicyclic precursor.     

Total synthesis of janadolide

The first total synthesis of janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, is described. The synthesis of an unsaturated hydroxycarboxylic acid was effected via the lithiation of vinyl iodide followed by addition to a Weinreb amide with a tert-butyl group and stereoselective 1,2-reduction. The cyclic structure was constructed by macrolactamization at the amide bond between the proline moiety and fatty acid moiety.     

Total synthesis of pulverolide: revision of its structure

A flexible and practical strategy toward the synthesis of rare 2H-furo[3,2-b]benzopyran-2-one skeleton has been developed. With a microwave-assisted cyclization-dehydration as the key transformation, the first total synthesis of pulverolide has been completed in 10 steps with 9% overall yield, leading to the revision of its proposed structure.     

Total synthesis of two natural phenanthrenes: confusarin and a regioisomer

The title compounds were synthesized by radical cyclization of the corresponding stilbenes intermediates. The latter ones arose from a Wittig reaction in a stereoselective manner (Z isomer is either the only one or the major one). Confusarin (1) was prepared in 13 steps from gallic acid. Its regioisomer (2) was obtained in five steps from syringaldehyde.     

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.     

Total synthesis of (±)-xanthocidin using FeCl3-mediated Nazarov reaction

The total synthesis of the antibiotic, (±)-xanthocidin (1), is described. The FeCl₃-promoted fast Nazarov reaction of the β-alkoxy divinyl ketone in the presence of t-BuOH provided the α-exo-methylene cyclopentenone, which is the core skeleton of this natural product. After methoxymethyl (MOM) esterification and protection of the reactive exo-methylene unit with a phenylseleno group, dihydroxylation, followed by oxidation, gave xanthocidin MOM ester. Finally, this ester was converted into (±)-xanthocidin (1) under mild conditions.     

Total synthesis of (3S,4S,2′S)- and (3R,4R,2′S)-viridiofungin A triester

The total synthesis of an alkylcitrate secondary metabolite from the fungi Trichoderma viride is described. An ester dienolate [2,3]-Wittig rearrangement and a S. Julia-Kocienski olefination served as key C/C-connecting transformations. The highly convergent synthesis consists of a longest linear sequence of 17 steps.     

Total synthesis of glypetelotine

A total synthesis of glypetelotine, the first sulphur-containing indole alkaloid from the leaf extracts of Glycosmis petelotii collected in the north of Vietnam, was described from indole through 6 steps. The structure of the glypetelotine was confirmed by IR, 1H NMR, 13C NMR and MS analysis. The spectral data of synthetic compound was identical with those of natural compound.     

Total synthesis of the potent anti-inflammatory lipid mediator Protectin D1

The total synthesis of the potent anti-inflammatory lipid mediator Protectin D1 derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C10 and C17 were obtained via a chiral pool strategy from (4R)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane and 3,4-O-isopropylidene-2-deoxy-d-ribose, respectively. Wittig reactions, Takai olefination, Pd⁰/Cu^I Sonogashira coupling, and Zn(Cu/Ag) reduction completed the total synthesis of Protectin D1.