Asymmetric synthesis of naturally occurring spiroketals

Spiroketals are widely found as substructures of many naturally occurring compounds from diverse sources including plants, animals as well as microbes. Naturally occurring spiroketals are biologically active and most of them are chiral molecules. This article aims at reviewing the asymmetric synthesis of biologically active spiroketals for last 10 years (1998-2007).     

A convenient synthesis of naturally occurring quinizarins

A general and regiospecific method for the preparation of quinizarins involves the cycloaddition of electron-rich dienes. Advantageous syntheses of several natural products, 2-methylquinizarin, islandicin, digitopurpone, erythroglaucin, 5-0-methylislandicin and 8-0-methyl-digitopurpone illustrate this procedure. A structure attributed to ventinone B is incorrect and 1,4,8-trihydroxy-6-methylanthraquinone is different from a natural substance so described.     

Photochemical synthesis of naturally occurring β-diketones

Photochemical syntheses of pongamol, ovalitenone, and milletone from the corresponding 2′-methoxychalcone epoxides are reported.     

Chemoenzymatic synthesis of naturally occurring benzyl 6-O-glycosyl-beta-D-glucopyranosides

Direct beta-glucosidation between benzyl alcohol and D-glucose (5) using the immobilized beta-glucosidase from almonds with the synthetic prepolymer ENTP-4000 gave a benzyl beta-D-glucoside (1) in 53% yield. The coupling of the benzyl beta-D-glucopyranoside congener (8) derived from 1 with phenyl 2,3,4-tri-O-acetyl-1-thio-beta-D-xylopyranoside (9), ethyl 2,3,4-tri-O-acetyl-1-thio-alpha-L-rhamnopyranoside (13), and 2,3,4-tri-O-acetyl-alpha-L-arabinopyranosyl bromide (15) afforded 10, 14, and 16, respectively, as coupled products. Deprotection of 10, 14, and 16 provided the synthetic benzyl beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside (2), benzyl alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3), and benzyl alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside (4), respectively.     

三种O－异戊烯基苯丙素类天然产物的首次合成

以香草醛为起始原料，经O－异戊烯基化、Witting反应、水解、还原、氧化等 反应步骤，首次合成了三种苯丙素天然产物boropinalA（1），boropinalC（2） boropinicAcid（3）,有化合物结构均由核磁共振氢谱，质谱及红外光谱确证，用 X射线衍射法测定了3的晶体及分子结构。     

Facile synthesis and antibacterial activity of naturally occurring 5-methoxyfuroflavone

A convenient synthesis of 5-methoxyfuroflavone (6, pongaglabol methyl ether), a constituent of some Pongamia or Millettia genus, was achieved by starting from 2,4-dihydroxy-6-methoxyacetophenone via a chalcone precursor, followed by treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). This five-step reaction (total yield: 21.6%) is more facile with that of previously utilized procedures using each different starting material. Antibacterial activities of the above compound and its precursor chalcones, which also belongs to the class of furoflavonoids, were tested by the disc diffusion method against Shigella dysenteriae, Salmonella typhi, Streptococcus-β-haemolyticus, and Staphylococcus aureus. 5-Methoxyfuroflavone showed moderate bactericidal activity against all tested bacterial strains, whereas its corresponding chalcone compound revealed a selective activity.     

Total synthesis of naturally occurring cephalosporolides E/F

A modular total synthesis of cephalosporolides E/F featuring sequential epoxide–alkyne coupling and subsequent highly regioselective gold catalyzed alkynolcycloisomerization of the resulting alkynetetrol to construct the central spiroketal core has been documented.     

Carbohydrate-based synthesis of naturally occurring marine metabolites slagenins B and C

[reaction: see text] The first enantioselective syntheses of slagenins B and C, marine metabolites from Agelas nakamurai, starting from L-arabinose have been described.     

An efficient and enantioselective total synthesis of naturally occurring L-783277

Naturally occurring L-783277 which belongs to 14-membered resorcylic acid lactones (RALs) turned out to be a potent kinase inhibitor against MEK (MAP kinase kinase). We successfully accomplished efficient and enantioselective total synthesis of L-783277 based on convergent assembly of one aromatic unit and two chiral building blocks with efficient orthogonal protection-deprotection strategy. Three key steps composed of olefin cross metathesis, addition of acetylene derivative to aldehyde, and Yamaguchi macrolactonization were subsequently employed to construct the framework of L-783277. The optical rotation value of L-783277 is for the first time presented in this Letter.     

A novel and efficient synthesis of the naturally occurring nucleoside doridosine

1-Methylisoguanosine was synthesized by a one-pot reaction involving a condensation of 5-amino-1-(β-$\text{D}$-ribofuranosyl)imidazole-4-carboxamide (1) with methyl isothiocyanate, treatment of the resulting thiourea derivative with DCC furnished 5-(3-methyl-1-ureido)-1-(β-$\text{D}$-ribofuranosyl)imidazole-4-carbonitrile (4) which was then annulated with ethanolic ammonia to furnish doridosine in a 68% yield from 1.     

Concise formal total synthesis of hybocarpone and related naturally occurring naphthazarins

A concise formal total synthesis of the cytotoxic bisnaphthazarin derivative hybocarpone has been completed through the development of routes to the synthetic precursor, 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone. The oxidation of 3-ethyl-1,2,4,5,7,8-hexamethoxy-6-methylnaphthalene under Rapoport conditions gave 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone in modest yields after basic hydrolysis. In addition, treatment of 3-ethyl-1,2,4,5,7,8-hexamethoxy-6-methylnaphthalene with boron tribromide provided access to the naturally occurring naphthazarin, boryquinone. The analogous oxidative demethylation of 3,6-dimethyl-1,2,4,5,7,8-hexamethoxynaphthalene and 3-ethyl-1,2,4,5,7,8-hexamethoxynaphthalene resulted in the synthesis of 2,5,7,8-tetrahydroxy-3,6-dimethyl-1,4-naphthoquinone (aureoquinone) and 3-ethyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone, respectively. An alternative selective synthetic route to 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone was also developed utilizing an intramolecular Claisen condensation of methyl 2-butyryl-3,5,6-trimethoxy-4-methylphenylacetate with concomitant in situ aerial oxidation.     

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.     

Regiospecific synthesis of isopestacin, a naturally occurring isobenzofuranone antioxidant

A DBU promoted aldol cyclocondensation of hydroxyisobenzofuranone 15 with cyclohexane-1,3-dione, followed by aromatization has resulted in the first short synthesis of isopestacin (1).     

Efficient total synthesis of naturally occurring anti-TMV compound gramniphenol G

An efficient synthesis of Gramniphenol G identified as 2-(4′-Methoxyphenyl)-7,7-dimethyl-7H-furo[3,2-g]chromene and originally isolated from the plant Arundina gramnifolia belonging to orchidaceae family was accomplished starting from resorcinol. The key step involves the oxidative cyclization of o-vinyl phenol to provide benzofuran moiety.     

Stereoselective synthesis of the naturally occurring styryllactones (+)-goniofufurone and (+)-cardiobutanolide

The naturally occurring gamma-lactones (+)-goniofufurone 1 and (+)-cardiobutanolide 2, two pharmacologically active products from Goniothalamus species (Annonaceae), have been synthesized in enantiopure form using l-erythrulose as the chiral starting material. Key steps of these syntheses were a stereoselective anti boron aldol reaction and an asymmetric allylboration.     

Total synthesis of naturally occurring chiral cyclopropane fatty acids and related compounds

Cyclopropane fatty acids (CFAs) and related compounds containing CFAs commonly occur in various natural sources, including plants or microorganisms. Some CFAs exhibit intriguing biological activities such as antifungal or immunosuppressive activities. Due to their biological importance and structural features, a number of synthetic studies have been conducted to date. These total syntheses have helped to elucidate their structural determinants or biological activities. Herein the total syntheses of naturally occurring CFAs and related compounds are summarized.     

Facile synthesis of new oxalate dimers of naturally occurring 3-hydroxysteroids

Several symmetrical steroidal oxalate dimers were synthesised from naturally occurring 3-hydroxysteroids, namely, estrone (1), DHEA (3), pregnenolone (5), cholesterol (7), 5D-cholestane (9), and stigmasterol (11), using oxalyl chloride. Full spectroscopic data for all the new compounds are presented. Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 442–444, September–October, 2006.     

Stereoselective synthesis and structural correction of the naturally occurring lactone stagonolide G

A convergent synthesis of the structure proposed for the naturally occurring lactone stagonolide G is described. All three stereocenters were created with the aid of asymmetric Brown allylations. The lactone ring was built by means of a ring-closing metathesis (RCM). The synthetic and the natural compound differed in their spectral properties. A new structure is now proposed for stagonolide G and demonstrated by means of a chemical transformation.