Protecting group directed stereoselective reduction of an epi-inosose: efficient synthesis of epi-inositol

A facile and high yielding synthesis of epi-inositol via stereoselective reduction of a pentaprotected epi-inosose is reported. Extent of stereoselectivity during the hydride reduction appears to depend on the ability of the substrate to complex with metal ions in the reducing agent.     

Asymmetric synthesis of the tetrahydropyran ring, C32-C38 fragment, of phorboxazoles

The asymmetric synthesis of a model aldehyde (2R,6R)-2 and the C32-C38 fragment of phorboxazoles, (2R,4R,6R)-1, is described using a sulfoxide as chiral auxiliary. Key advances include the stereoselective reductions of beta-keto- or beta,gamma-diketosulfoxides, the acid-catalyzed cyclization of enantiopure sulfinyl hydroxy ketone precursors to the tetrahydropyran ring, and the Pummerer reaction on the pendant sulfoxide to create the formyl group.     

Stereoselective synthesis of the tetrahydropyran core of polycarvernoside A

[reaction: see text] A concise and stereoselective synthesis of the tetrasubstituted tetrahydropyran core of polycavernoside A was achieved in 55% overall yield from 3-benzyloxypropanal. A stereoselective allyl transfer reaction was used in the synthesis of enol ether 18 followed by a TFA-mediated cyclization to create the three new asymmetric centers in the tetrahydropyran with complete stereocontrol in a single-pot process.     

Synthetic studies on (+)-naphthyridinomycin: stereoselective synthesis of the tetracyclic core framework

[reaction: see text] The stereoselective synthesis of the tetracyclic intermediate 21 for (+)-naphthyridinomycin (1) has been accomplished. The convergent synthesis used the Ugi 4CC reaction with the amine derivative 10. The key features of the stereoselective synthesis of 21 were the intramolecular Mizoroki-Heck reaction, an aromatic-aldehyde cyclization, and a stereoselective hydroboration.     

Synthetic studies toward merrilactone A: a short synthesis of AB ring motif

An efficient route to the AB ring motif of merrilactone A has been established by remarkable regioselective reduction of cyclic anhydrides 3 and 8 to the γ-lactone moiety, followed by the successive Stille and Heck reactions of 1,1-dibromo-1-alkene.     

Synthetic studies on (+)-manzamine A: stereoselective synthesis of the tetracyclic core framework

The stereoselective synthesis of the tetracyclic intermediate 3 for (+)-manzamine A (1) has been achieved. The key features of this stereoselective synthesis of 3 are the Rh-catalyzed asymmetric hydrogenation and a diastereoselective intermolecular Diels-Alder reaction. The 8-membered ring is efficiently constructed utilizing our Ns-strategy.     

Synthetic studies on statins. Part 1: a short and cyanide-free synthesis of atorvastatin calcium via an enantioselective aldol strategy

A short and cyanide-free enantioselective synthesis of atorvastatin calcium has been achieved starting from a commercially available highly substituted 1,4-diketone in an overall yield of 40%. The key step in this approach is the asymmetric aldol reaction of an aldehyde with diketene in the presence of Ti(O-i-Pr)₄–Schiff base complex to create the (5R)-stereochemistry of atorvastatin calcium.     

Synthetic studies on Et-743. Assembly of the pentacyclic core and a formal total synthesis

A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.     

A biomimetic type expedient approach to the tricyclic core of xyloketals. Application to a short, stereocontrolled synthesis of alboatrin and a remarkable epi to natural isomerisation

An expedient synthesis of the linear tetrahydrofurano benzopyran ring system of xyloketals is described involving an ortho ester Claisen rearrangement and an intramolecular cationic cyclisation. This strategy was applied for a short, stereocontrolled and high yield synthesis of the phytotoxic metabolite alboatrin.     

Synthetic studies on altemicidin: stereocontrolled construction of the core framework

The stereoselective synthesis of the key intermediate for altemicidin has been accomplished. The synthesis commenced with a bicyclo[3.3.0] framework, which was readily obtained via an intramolecular C-H insertion reaction. A Curtius rearrangement was employed as a key step to stereoselectively construct the beta-hydroxyl alpha-disubstituted-alpha-amino acid structure. Synthesis of vinylogous urea was achieved using hydrolysis of nitrile intermediate.     

Synthetic studies on chartelline C: stereoselective construction of the core skeleton

What a core-ker! The title synthesis was achieved using a route featuring an intramolecular Mitsunobu reaction of a nosyl amide, stereoselective construction of the β-lactam, and formation of an enamide moiety by selenoxide elimination. The stereochemistry of the alkylation for the formation of the β-lactam was controlled by a secondary hydroxy group on the ten-membered ring. SEM=2-(trimethylsilyl)ethoxymethyl; TBS=tert-butyldimethylsilyl.     

Synthetic studies towards Chlorahololides A: practical synthesis of a lindenane-type sesquiterpenoid core framework with a 5,6-double bond

Towards Chlorahololides A: a lindenane-type sesquiterpenoid framework that contains a 5,6-double bond was synthesized from simple starting materials. The reductive cyclization of a 1,6-enyne and an unusual endo-type intramolecular Heck reaction was used as key steps for ring closure.     

Enantioselective synthesis of epi-(+)-Sch 642305: observation of an interesting diastereoselection during RCM

In an approach towards the enantioselective total synthesis of the novel bioactive natural product Sch 642305, an unusual diastereoselection during the key RCM reaction, resulted in the synthesis of the 11-epi-isomer of Sch 642305.     

Strategy for synthesis of the isoleucine conjugate of epi-jasmonic acid

The TES ether of 2-((1R,2S,3R)-3-hydroxy-2-((Z)-pent-2-enyl)cyclopentyl)acetic acid (5, equal to the reduction product of epi-jasmonic acid) derived from (1R,4S)-4-hydroxycyclopent-2-enyl acetate (19) in 13 steps was activated by using isobutyl chloroformate and was subjected to condensation with isoleucine at room temperature for 48 h. The product was desilylated and oxidized to the isoleucine conjugate of epi-jasmonic acid in 68% yield over three steps. Similarly, allo-isoleucine conjugate of epi-jasmonic acid and three isoleucine conjugates of ent-epi-jasmonic acid, jasmonic acid, and ent-jasmonic acid were synthesized.     

Synthetic studies toward the total synthesis of tedanolide: assembly of the C1-C23 carbon backbone

A stereoselective assembly of the C1-C23 fragment representing the carbon backbone of tedanolide was accomplished utilizing a chiral boron reagent to effect the aldol coupling of the C1-C12 diketoester fragment with the C13-C23 aldehyde fragment.     

Synthetic studies toward macrocidins: an RCM approach for the construction of the central cyclic core

The central macrocyclic core of the macrocidins was constructed using RCM as the key reaction. A preliminary investigation dealing with the key reactions, that is, the Dieckmann cyclization and the RCM, revealed that RCM of the β-ketoamide is better than RCM of the corresponding acyltetramic acid.     

Synthesis of the dysiherbaine tetrahydropyran core employing a tethered aminohydroxylation reaction

A stereocontrolled and scalable synthesis of an advanced intermediate of the dysiherbaine tetrahydropyran core has been achieved in 11 steps and 27% overall yield. The key feature of this synthetic approach is the application of the Donohoe tethered aminohydroxylation reaction to install the amino diol and establish the four contiguous syn stereocenters on the tetrahydropyran ring.     

Synthetic studies on jadomycins: synthesis of dimethyljadomycin A

Dimethyljadomycin A was synthesized as the first example for the construction of 8H-benzo[b]oxazolo[3,2-f]phenanthridine skeleton.     

Synthetic studies on amipurimycin: total synthesis of a thymine nucleoside analogue

Amipurimycin, a member of the complex peptidyl nucleoside family of antibiotics, is a Streptomyces-derived potent antifungal agent. The mechanism of action of amipurimycin, however, remains undetermined. Additionally, there are no reports on the total synthesis or structure-activity relationships (SAR) of this potentially useful bioactive compound. In a study aimed at the total synthesis and SAR studies of this natural product, the present research reports the development of a synthetic route to the central pyranosyl amino acid core of amipurimycin and its further elaboration, culminating in the synthesis of a unique thymine analogue. Utilizing a d-serine-derived dihydroaminopyrone as a strategic building block, the synthesis involves de novo construction of the fully functionalized C-3-branched carbohydrate amino acid core, followed by glycosidic attachment of thymine at C-1, and peptidic linking of the C-6 amine with the 1,2-aminocyclopentane carboxylic acid side chain.