‘One-pot’ four-step synthesis of cerpegin

Cerpegin (1) was synthesized through a ‘one-pot’ reaction in 71% overall yield. Lithiation of commercially available 2-methoxynicotinic acid (2) as its lithium salt using LTMP, followed by addition of acetone at low temperature and a specific acidic treatment of the intermediate 3 thus obtained, gave the 1,1-dimethyl-3,4-dioxo-1,3,4,5-tetrahydrofuro[3,4-c]pyridine (4). The latter was finally selectively alkylated using methyl iodide and caesium carbonate to afford cerpegin (1).     

A short synthesis of de-‘prenyl’-ardeemin

A four-step synthesis of the ardeemin framework by starting from N-2-aminobenzoyl-α-amino esters is described. In the last step, the acid promoted cyclization of the 1,4-anti-4-alkyl-1-(3-indolylmethyl)-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones occurs irreversible and stereocontrolled.     

Diversity‐oriented synthesis

Diversity‐oriented synthesis (DOS), which describes the synthesis of structurally diverse collections of small molecules, was developed, in part, to address combinatorial chemistry's shortfalls. In this paper, we hope to give an indication of what can be achieved using the DOS approach to library generation. We describe some of the most successful strategies utilized in DOS, with special focus on our own area of interest; DOS from simple, pluripotent starting materials. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 129–142; 2008: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20144     

‘Click’ synthesis of triazole-based spirostan saponin analogs

Novel analogs of spirostan saponins in which the glycosidic bond has been replaced by a triazole linkage are described. For this, a direct oligosaccharide-steroid conjugation approach based on the Cu^I-catalyzed azide-alkyne 1,3-dipolar cycloaddition was implemented, leading to diverse combinations of saponin analogs with variations in the trisaccharide moiety, the artificial linkage, and the steroid-skeleton functionalization. This ‘click’ process proved great efficiency for the ligation of two bulky building blocks (e.g., chacotriose derivatives and spirostanes bearing axial azides), which enabled the rapid creation of a small library of triazole-based analogs for cytotoxicity evaluation. A molecular modeling study was performed to understand the conformational and electronic differences between a natural saponin and its triazole-based analogs.     

Photochemical synthesis of gold–polyethylenglycol core–shell nanoparticles

A new, fast and convenient method for the preparation of gold–polyethylenglycol core–shell nanoparticles in water was described. The method pertains to the concomitant redox and polymerization reactions of the acrylic formulation induced by photochemically generated radicals from the photoinitiator, 2-hydroxy-2-methyl-1-phenyl-1-propanone. The nanoparticles were characterized by using Dynamic Light Scattering (DLS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). Homogenous core–shell structured nanoparticles obtained this way are expected to find important applications in bio-medical fields.     

Polyhydroxylated indolizidine alkaloids—synthesis of dideoxycastanospermine

The key transformation developed in this work is the anti-Kishi selective dihydroxylation, which proceeds by way of intramolecular participation of the nitrogen protecting group to furnish the desired stereochemistry required for castanospermine like structures. In this paper, we completed a first synthesis of a novel dideoxycastanospermine 6.     

Microwave-assisted synthesis of 4,4′-diaminotriphenylmethanes

A fast, efficient and versatile route of synthesis of 4,4′-diaminotriphenylmethanes under microwave irradiation, suitable for parallel library syntheses were developed.     

A convergent total synthesis of ouabagenin

A convergent total synthesis of ouabagenin, an aglycon of cardenolide glycoside ouabain, was achieved by assembly of the AB-ring, D-ring and butenolide moieties. The multiply oxygenated cis-decalin structure of the AB-ring was constructed from (R)-perillaldehyde through the Diels–Alder reaction and sequential oxidations. The intermolecular acetal formation of the AB-ring and D-ring fragments, and combination of the intramolecular radical and aldol reactions, assembled the requisite steroidal skeleton in a stereoselective fashion. Finally, stereoselective installation of the C17-butenolide via the Stille coupling and hydrogenation led to ouabagenin.     

Stereoselective synthesis of (−)-allosedamine

A stereoselective synthesis of (−)-allosedamine is disclosed. β-Aminosulfoxide 4 was generated stereoselectively by condensation of the sulfinyl anion 2 with N-Ts imine 3. The bromohydrin 5 was obtained by intramolecular sulfinyl group participation and the piperidine ring of allosedamine was elaborated using the ring-closing metathesis (RCM) reaction.     

Total synthesis of (±)-pentenomycin

A concise stereoselective route to (±)-pentenomycin 1 in 33% overall yield starting from the readily accessible Diels-Alder adduct 4 is reported. The key reaction involves decarbonylation of β-methoxy-α,β-unsaturated aldehyde 8 obtained from β-hydroxy-dimethylketal 6.     

Total synthesis of (±)-antofine

An efficient preparation of (±)-antofine is described. The main steps involved in this synthesis are the Horner–Wadsworth–Emmons reaction, the intramolecular Schmidt reaction of an azido aldehyde, and the one-pot deprotection of the N-formyl group, followed by Pictet–Spengler cyclization. The asymmetric hydrogenation of the trisubstituted α,β-unsaturated ester is also explored, however only moderate enantio-control (55% ee) is obtained. Finally, (±)-antofine is prepared in six steps from the phenanthryl aldehyde 5 with an overall yield of 35%.     

Stereoselective synthesis of nucleoside monophosphate HepDirect™ prodrugs

Synthesis of HepDirect™ prodrugs of nucleoside monophosphates via phosphorylation with a chiral reagent forms a new asymmetric center at phosphorus and produces two diastereomers. Coupling of chiral phosphoramidite 6 derived from (S)-diol 5 with ara-A followed by oxidation of the intermediate phosphite gave ara-AMP prodrugs 8 (4S,2S isomer) and 9 (4S,2R isomer). Several methods were explored to identify routes for the selective synthesis of each diastereomer. Two successful stereoselective approaches to ara-AMP prodrugs 8 and 9 are described.     

Facile synthesis of 3‐spiroindolines

Cyanoacetyldiazoindol‐2‐one ( 3 ), the condensation product of cyanoacetohydrazide with isatin ( 1 ), could be cyclized in acidic medium via its CN group and its enolic OH to give cyanomethyloxadiazole‐spiroindoline ( 4 ). The presence of the methylcyano side chain could be invested—through oximation, diazotization, or condensation with aldehydes—to form polyfunctional spiroindolines 5, 8–10 . Also, a second route for preparing the title compound could be achieved through a nucleophilic attack on position 3 in the isatin derivatives, followed by subsequent ring closure to give 6 and 7 . © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:207–210, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10020     

A practical synthesis of 4′-thioribonucleosides

A practical synthesis of 4′-thioribonucleosides starting from inexpensive l-arabinose is described. 1,4-Anhydro-2,3-O-isopropylidene-4-thioribitol, which was prepared by using a novel reductive ring-contraction reaction, was converted to the 5-O-silylated sulfoxides. The Pummerer-type thioglycosylation of the sulfoxides gave the 4′-thioribonucleosides stereoselectively.     

Total synthesis of (±)-protoemetinol

A new approach to the benzo[a]quinolizidine alkaloid was described. Total synthesis of (±)-protoemetinol (1) was reported.     

Asymmetric synthesis of (−)-codonopsinine

The asymmetric synthesis of (−)-codonopsinine was achieved in 7 steps (from commercially available tert-butyl crotonate) in 5% overall yield and >99:1 dr. The key step in this synthesis involved ring-closing iodoamination of a functionalised homoallylic amine, which occurred with concomitant N-debenzylation, to give a 3-iodopyrrolidine that was elaborated to (−)-codonopsinine.     

Total synthesis of biseokeaniamides A–C and late-stage electrochemically-enabled peptide analogue synthesis

The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A–C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation–nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for building block syntheses. Electrochemically-generated N,O-acetal intermediates are engaged with electron-rich aromatics and organometallic reagents to forge modified amino acids and peptides. The value of this late-stage modification method is highlighted by the expedient and divergent production of bioactive peptide analogues, including compounds which exhibit enhanced cytotoxicity relative to the biseokeaniamide natural products.

A late-stage electrochemical decarboxylation enables rapid access to structural analogues of biseokeaniamides A–C, cytotoxic lipopeptide natural products.     

Total synthesis of (−)-centrolobine

Stereoselective synthesis of (−)-centrolobine, an anti-Leishmania agent, was accomplished via an intramolecular Barbier-type reaction of iodo-ester with n- or t-butyllithium followed by Lewis acid-promoted Et₃SiH reduction of the resulting hemiacetal.     

New synthesis of oxindole‐1‐carboxamides

A new synthesis of oxindole‐1‐carboxamides was elaborated by the reaction of oxindole‐1‐phenyl‐carboxylate with various amines. This method also permitted the preparation of N,N‐disubstituted oxindole‐1‐carboxamides.