The synthesis of (−)-cis- and (−)-trans-crobarbatic acid

The synthesis of both cis- and trans-crobarbatic acid is reported. The five-step sequence proceeds in high yield and with control of both relative and absolute stereochemistry. The key step in the synthesis is the Birch reductive alkylation of a chiral furoic acid which sets the absolute stereochemistry of the products. The stereochemistry of the compounds described was proven unambiguously by X-ray crystallography on one synthetic intermediate and on trans-crobarbatic acid.     

Asymmetric synthesis of 2-alkyl-substituted 2-hydroxyglutaric acid γ-lactones

3-Alkyl-1,2-cyclopentanediones 1 are transformed into 2-alkyl-2-hydroxyglutaric acid γ-lactones 3 in up to 83% isolated yields and up to 96% ee, affording a simple access to many bioactive compounds, including diacylglycerol lactones (DAG-lactones).     

Synthesis of γ-lactones by desymmetrization. A synthesis of (−)-muricatacin

A short synthesis of the natural potent cytotoxic agent (−)-muricatacin 1 and related unsaturated lactones from a versatile common intermediate, dienedioate 2, derived from d-mannitol or tartaric acid, is described. The strategy depends upon the desymmetrization of 7 by dihydroxylation and elaboration of the hydroxy alkyl sidechain. A route to unsaturated lactones is also described using a cis selective Wittig reaction. Since the enantiomers of 2 are available from the corresponding tartaric acids, this method provides access to both enantiomers of the described compounds and a wide range of derivatives.     

An efficient stereocontrolled synthesis of (−)-10-epi-5β,11-dihydroxyeudesmane and (−)-4,10-epi-5β,11-dihydroxyeudesmane

A concise and efficient synthesis of (−)-10-epi-5β,11-dihydroxyeudesmane 1 and (−)-4,10-epi-5β,11-dihydroxyeudesmane 2, via (−)-10-epi-γ-eudesmol 5, was accomplished starting from (+)-dihydrocarvone. The salient feature of our synthesis is the utilization of substrate-directable epoxidation and homogeneous hydrogenation to control the stereochemistry at the C-4 and C-5 positions of the title compounds.     

Enantioselective synthesis of herbertane sesquiterpenes: synthesis of (−)-α-formylherbertenol

The synthesis of 4-hydroxy-3-[(1S)-1,2,2-trimethylcyclopentyl]benzaldehyde [(−)-α-formylherbertenol 1], a herbertane-type sesquiterpene isolated from the leafy liverwort Herberta adunca, from β-cyclogeraniol is described. The synthesis is based on the previously described preparation of an enantiopure 1,2,2-trimethylcyclopentane synthon from which the characteristic aromatic moiety of 1 is elaborated, using a Robinson annulation and a palladium-catalysed methoxycarbonylation of an aryl triflate as key synthetic steps. The synthesis of the natural sesquiterpene (−)-α-herbertenol, also a natural sequiterpene, using the same methodology is also described.     

A stereocontrolled synthesis of (−)-detoxinine from l-ascorbic acid

A stereoselective synthesis of (−)-detoxinine, the core unit of the detoxifying agent detoxin D₁, is presented. The approach, characterized by the use of an inexpensive starting material and by the easy and stereoselective preparation of the key 4,5-disubstituted oxazolidin-2-one 11, proves to be a suitable alternative to the known procedures.     

Enantioselective synthesis of (−)-γ-jasmolactone

The title compound was prepared in seven steps starting from the commercially available 4-ketopimelic acid. The key step features an enantioselective lactonization promoted by PPL.     

Enantioselective synthesis of functionalized γ-butyrolactones

Sharpless asymmetric dihydroxylation and aminohydroxylation of (E)-dimethyl-2-alkylidene glutarates 2 were shown to afford enantio-enriched or enantiopure highly functionalized γ-butyrolactones 3 and 7.     

Enantioselective formal synthesis of (−)-ovalicin using quinic acid as a chiral template

The key intermediate 18 for the synthesis of (−)-ovalicin was synthesized using (−)-quinic acid as the chiral source, through a series of stereocontrolled and efficient chemical reactions, thus establishing a new, formal synthesis of the natural target. The featuring spirocyclic epoxide function has been installed by internal Williamson ether synthesis using the functionalities originally present at C-1 of (−)-quinic acid after the appropriate adjustments required to introduce the necessary functionality at C-2.     

Enantioselective synthesis of the quinolizidine alkaloids (+)-myrtine and (−)-epimyrtine

The enantioselective synthesis of (+)-myrtine 1 and (−)-epimyrtine 2 is described starting from (S)-2-(2-hydroxypropyl)allyltrimethylsilane 4 using an intramolecular allylsilane N-acyliminium ion cyclization.     

Meldrum's acid — A reagent for the synthesis of unsaturated γ-lactones and Β-acylacrylic acids

The thermal cyclization of 2,2-dimethyl-5-(2-aryl-2-oxoethyl)-1,3-dioxan-4,6-diones forms 5-aryl-, butenolides. Regioselective chlorination of 2, 2-dimethyl-5-[2-aryl(alkyl)-2-oxoethyl]-1,3-dioxane-4,6-diones by SO₂Cl₂ gives the 5-chloro derivatives; these are cleaved by aqueous AcOH to the E--acylacrylic acids, which are synthones for unsaturated -lactones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp.1212–1214, May, 1991.     

Total Syntheses of (−)-Secologanin, (−)-5-Carboxystrictosidine,and (−)-Rubenine

The first enantioselective total syntheses of (−)-secologanin ( 1 ), (−)-5-carboxystrictosidine ( 2 ), and (−)-rubenine ( 3 ) were accomplished in 10, 9, and 14 steps, respectively. The key transformation in the synthesis of 1 was a sequential anti-selective organocatalytic Michael reaction/Fukuyama reduction/spontaneous cyclization to form an optically active dihydropyran ring. In addition, the secologanin tetraacetate ( 16 ), which is a potential key intermediate for the bioinspired divergent syntheses of monoterpenoid indole alkaloids, was prepared in gram-scale in seven steps. The total syntheses of 2 and 3 , which are classified as glycosylated monoterpenoid indole alkaloids, were achieved through bioinspired transformations such as a diastereoselective Pictet–Spengler reaction, a site- and stereoselective epoxidation, and a site-selective epoxide ring-opening followed by a lactonization reaction.     

A biosynthetically inspired synthesis of (−)-berkelic acid and analogs

We describe a complete account of our total synthesis and biological evaluation of (?)-berkelic acid and analogs. We delineate a synthetic strategy inspired by a potentially biomimetic union between the natural products spicifernin and pulvilloric acid. After defining optimal parameters, we executed a one-pot silver-mediated in situ dehydration of an isochroman lactol to methyl pulvillorate, the cycloisomerization of a spicifernin-like alkynol to the corresponding exocyclic enol ether, and a subsequent cycloaddition to deliver the tetracyclic core of berkelic acid. Our studies confirm that the original assigned berkelic acid structure is not stable and equilibrates into a mixture of 4 diastereomers, fully characterized by X-ray crystallography. In addition to berkelic acid, C22-epi-berkelic acid, and nor-berkelic acids, we synthesized C26-oxoberkelic acid analogs that were evaluated against human cancer cell lines. In contrast to data reported for natural berkelic acid, our synthetic material and analogs were found to be devoid of activity.     

Enantioselective Synthesis and Racemization of (−)-Sinoracutine

Sinoracutine is a recently isolated alkaloid with unusual stereochemical and biological properties. It features an unprecedented tetracyclic 6/6/5/5 skeleton that bears an N-methylpyrrolidine ring fused to a cyclopentenone. Interestingly, both enantiomers of sinoracutine have been independently isolated from the same plant, yet the molecule does not appear to occur as a racemate. Here, we present a short synthesis of (−)-sinoracutine that relies on a highly diastereoselective Pauson–Khand reaction and a Mandai–Claisen reaction to install the quaternary stereocenter. Our work establishes the absolute configuration of the levorotatory isomer and suggests that the optical purity of sinoracutine varies in nature due to its gradual racemization. Experimental evidence supports this proposal, and a plausible mechanism for the racemization is provided.     

Total synthesis of (−) verbenalol and (−) epiverbenalol

The first asymmetric synthesis of (−) verbenalol and (−) epiverbenalol, starting from the organometallic complex (−) 1, is described.     

Regioselective fluorination in synthesis of deoxyfluoro quercitols from d-(−)-quinic acid

A facile synthesis of six new deoxyfluoro querciotls from d-(−)-quinic acid is described. The key steps involve the regioselective fluorination as well as highly stereoselective dihydroxylation. These synthetic deoxyfluoro quercitols are considered as potential glycosidase inhibitors.     

Enantioselective syntheses of (+)- and (−)-brazilin

Two enantiomers of brazilin were prepared in 9 steps from 7-hydroxychroman-4-one using the AD-mix-α and AD-mix-β-directed enantioselective dihydroxylation of 3-(4-hydroxy-3-methoxyphenyl)-2H-chromen-7-ol as a key step.     

Methyl 3-phenylsulphonyl orthopropionate: an efficient reagent for the synthesis of γ-lactones and butenolides

Treatment of methyl 3-phenylsulphonyl orthopropionate with n-BuLi gives the corresponding carbanion which reacts with aldehydes or ketones to yield β-phenylsulphonyl γ-lactones. Base-catalysed elimination of sulphinic acid yields α,β or β,γ-butenolides.     

Total Syntheses of (−)-Conidiogenone B, (−)-Conidiogenone,and (−)-Conidiogenol

Cyclopianes are novel diterpenes featuring a highly strained 6/5/5/5 tetracyclic core embedded with 6–8 consecutive stereocenters. The concise total syntheses of (−)-conidiogenone B, (−)-conidiogenone, and (−)-conidiogenol have been accomplished in 14–17 steps. The present work features a HAT-mediated alkene–nitrile cyclization to access the cis-biquinane, a Nicholas/Pauson–Khand reaction to construct the linear triquinane, and a Danheiser annulation to afford the congested angular triquinane skeleton.