Studies directed towards asymmetric synthesis of levobupivacaine

We report herein the first catalytic asymmetric synthesis of levobupivacaine. The key step involves the asymmetric alkylation of N-benzylimine glycinamide (2b).     

Studies directed towards the total synthesis of anthracycline antibiotics

At present anthracycline antibiotics have proven to be the most exciting agents in cancer chemotherapy. Both adriamycin and daunomycin are proven to be effective against a variety of human tumour cells, despite their cardiotoxicity. However, some synthetic analogues, such as 4-demethoxydaunomycin, are shown to be better therapeutic ratios compared to adriamycin or daunomycin. Various approaches have been successfully made for the total synthesis of (±) 4-demethoxydaunomycinone, the aglycone of (±) 4=demethoxydaunomycin, starting from benzoquinone, napthalene or anthraquinone precursors. Finally an elegant approach for the stereoconvergent synthesis of (+) 4-demethoxydaunomycinone has been worked out. New methods involving both Diels-Alder and Friedal-Crafts acylation, have been developed for the total synthesis of daunomycinone and 11-deoxydaunomycinone. The synthesis of L-daunosamine, the amino sugar unit present in the antitumor anthracyclines has been successfully elaborated starting either from D-glucose or D-glucosamine.     

Studies directed towards the total synthesis of morphine alkaloids

Application of metallated enamines to the synthesis of morphine related congeners is reported. A formal total synthesis of (±)-morphine has been completed.     

Synthesis of sesquiterpene antitumor lactones. 7. Studies directed toward the total synthesis of pentalenolactone. Intramolecular ene reaction.

Functionalized cyclopentene $\text{11}$ is cyclized via thermal ene reaction to $\text{12}$. All steps in the synthesis of $\text{12}$ are highly stereoselective.     

Stereospecific synthesis of γ-butyrolactones from acyclic vinyl sulfoxides: an asymmetric synthesis of optically pure oak lactones

The sulfoxide-directed lactonization of several trisubstituted vinyl sulfoxides with dichloroketene proceeds in a completely stereospecific manner. The lactonization of (E) -3 (R) -$\text{p}$-tolylsulfinyloctene occurs with complete enantiospecificity to produce a precursor for the synthesis of optically pure oak lactones.     

Synthesis of a key intermediate for the total synthesis of pseudopteroxazole

A facile synthesis of a key intermediate for the total synthesis of anti-mycobacterial compound pseudopteroxazole is described employing an intramolecular Diels-Alder cyclization and an iodine-mediated oxidative aromatization step.     

Studies towards the biomimetic synthesis of bisesquiterpene lactones

A possible biomimetic connection between atractylolide, hydroxyatractylolide and biatractylolide and biepiasterolide has been demonstrated by efficiently generating the biatractylolide and biepiasterolide core structures from atractylolide and hydroxyatractylolide model butenolides via a radicaloid intermediate in a single step in good yield.     

Studies directed towards the total synthesis of koshikalide: stereoselective synthesis of the macrocyclic core

The stereoselective synthesis of the macrolactone core of the natural product koshikalide is described. Starting with readily available 1,4-butanediol and malic acid as synthons, our synthetic strategy involved the reiterative application of Gilman’s reaction, Swern oxidation and Sharpless asymmetric epoxidation to establish the required stereocentres. Other key steps in the synthesis include Negishi cross coupling and Horner–Wadsworth–Emmons (HWE) reactions for construction of the main fragments. The 14-membered lactone ring was prepared by a selective Mitsunobu macrolactonization approach.     

Synthesis of a key intermediate for the total synthesis of streptovaricin A

A key intermediate ($\text{3}$) for the total synthesis of streptovaricin A ($\text{1}$) is synthesized in its optically active form. Further elaboration of $\text{3}$ is also described.     

Synthesis of the optically active key intermediate of FR901483

Efficient synthesis of the tricyclic key intermediate 2 for (−)-FR901483 1 was accomplished. The precursor of the intramolecular aldol reaction 4b is constructed by the Ugi 4CC reaction and subsequent intramolecular Dieckmann condensation. This approach allows a fully stereocontrolled total synthesis of (−)-FR901483, which would provide various derivatives.     

Studies directed towards the total synthesis of clavosolides: synthesis of an isomer of clavosolide A

The total synthesis of clavosolide A, employing a radical-mediated route to build its substituted tetrahydropyran unit, a Yamaguchi reaction to construct the diolide aglycon and the Schmidt method for the final glycosidation step, revealed that the reported structure is an isomer of the natural product.     

An asymmetric route to total synthesis of the furano lignan (+)-veraguensin

Total synthesis of the furano lignan (+)-veraguensin is described. The key steps involve a diastereoselective aldol-type condensation of an ester enolate having an α-chiral center with an aromatic aldehyde and a novel isomerization of the syn vicinal substituents on the furan ring via a ring opening-ring closing protocol.     

Stereochemical studies-LVIII: Synthesis of optically active compounds by the novel use of meso-compound-2. efficient synthesis of an optically pure steroid intermediate

In order to explore the general application of a novel method for preparing optically active compounds, synthesis of the optically pure steroid intermediate((?)-1) has been examined by employing the diol(2) as a meso-compound and N-mesyl-(S)-phenylalanyl chloride(3) as a source of the optically active functional group.     

Studies directed toward the total synthesis of discodermolide: asymmetric synthesis of the C1-C14 fragment

[structure: see text] A convergent and stereoselective assembly of the C1-C14 subunit of marine natural product (+)-discodermolide has been completed. The approach employs chiral allylsilane bond construction methodology to establish four of the eight stereogenic centers. Key fragment coupling is achieved via an efficient stereoselective acetate aldol reaction between C1-C6 and C7-C14 subunits.     

Heterocycles. XXVI. A total synthesis of optically pure (+)-catechin pentaacetate

A total synthesis of optically pure (+)-catechin pentaacetate has been established using the (-)-chalcon epoxide (100% ee) derived from 3,4,2′,4′,6′-pentakis(methoxymethoxy)chalcon as the starting material. The optical purity of the product is confirmed by ¹H nmr analysis in the presence of a shift reagent.     

Studies towards the total synthesis of contignasterol

The (17R,20S,22S,24S) C₂₀-C₂₉ segment of contignasterol has been stereoselectively prepared in 8 steps and 40% overall yield from (S)-carvone. Synthetic studies towards contignasterol's C/D ring functionalization/isomerization are also reported.     

Studies towards the total synthesis of Phostriecin

A synthetic approach toward the phostriecin, an antitumor natural product is described. The key features of the present synthesis are Wittig reaction, synthesis of homoallylic alcohol using Brown’s protocol (alkoxyallylboration) and RCM for the creation of unsaturated lactone moiety of phostriecin.