Total synthesis of (+)-peloruside A

[reaction: see text] A total synthesis of (+)-peloruside A has been successfully achieved. The strategy was highlighted by a late stage aldol coupling of two complex fragments followed by an intramolecular hemi-ketal cyclization, a MOM group participated epoxide ring fragmentation reaction, and a highly selective methylation. This convergent route allows access to rationally designed analogues.     

A stereoselective synthesis of the C11-C19 fragment of (+)-peloruside A

A new route to the synthesis of the C11-C19 fragment of peloruside A is described, which includes an aldol reaction with ethyl acetoacetate, β-hydroxyl-directed reduction of β-hydroxy ketone, as well as methylation of C13 hydroxyl moiety in the system of MeI-Ag₂O-MgSO₄-CH₂Cl₂.     

Toward the synthesis of (+)-peloruside A via an intramolecular vinylogous aldol reaction

The use of the intramolecular vinylogous aldol reaction for the preparation of an advanced intermediate for the synthesis of peloruside A is described. The reaction was applied to compound 19 and proceeds in high yield and good levels of diastereoselectivity. Application of the Achmatowicz reaction to this intermediate provided the corresponding pyranone, a late stage intermediate well positioned for conversion to the natural product.     

Cyloadditions of benzopyrones: Rapid access to bicyclic AB-ring analogues of anthracyclines

Cycloaddition of the benzopyrone 10b with 1,1-disubstituted alkenes 12, 14, and 16 produces fair yields of the lactones 13, 15, and 17, AB-ring analogues of the anthracyclines.     

Synthesis of the C12-C19 fragment of (+)-peloruside A through a diastereomer-discriminating RCM reaction

[reaction: see text]. A short and efficient asymmetric synthesis of the C12-C19 fragment of the cytotoxic macrolide (+)-peloruside A has been achieved via a highly diastereomer-discriminating RCM of alpha-branched but-3-enoate ester of a methallylic alcohol derived from hydrolytically resolved (S)-(-)-propylene oxide.     

A strategy to access fused triazoloquinoline and related nucleoside analogues

Fused triazoloquinolines have been prepared starting from (E)-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-ones and sugar or benzyl azides in a sequential [3+2] cycloaddition reaction, followed by one pot Pd–C assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N¹-glycosyl substituents as unnatural nucleosides have inherent potential to generate a library of compounds for bioevaluations.     

A facile two-step chemoenzymatic access to natural germination inhibitor (+)-erigeronic acid A

A facile two-step synthesis of natural germination inhibitor 5-butyl-3-oxo-2,3-dihydrofuran-2-yl-acetic acid [(+)-erigeronic acid A, 1] has been described via highly regioselective ring opening of (R)-acetoxysuccinic anhydride with the primary enolate of butyl methyl ketone, followed by an enzymatic hydrolysis and an in situ dehydrative cyclization pathway with 77% overall yield. On the basis of the present chemoenzymatic approach, (R)-configuration has been assigned to the C-2 chiral centre of the natural erigeronic acid.     

Rapid access to reactive polymer-supported isocyanates

Isocyanate resins are used in polymer assisted solution-phase synthesis, however, their use is limited by their high cost and often unfavourable reaction profiles. Here a route to prepare efficient supported isocyanate resins from aminomethyl resin and inexpensive diisocyanates is reported and compared to commercially available isocyanate resins.     

Rapid and efficient access to secondary arylmethylamines

Ammoniomethyl trifluoroborates are very powerful reagents that can be used to access biologically relevant aryl- and heteroaryl-methylamine motifs via Suzuki-Miyaura cross-couplings. Until now, this method was limited to the production of tertiary and primary amines. The synthesis of a large array of secondary ammoniomethyltrifluoroborates has been achieved through a one step nucleophilic substitution reaction on the potassium bromomethyltrifluoroborate. Smooth cross-coupling conditions have been designed, based on the use of an aminobiphenyl palladium precatalyst, to couple these trifluoroborates efficiently with aryl bromides. This strategy offers a new way to access biologically relevant motifs and allows, with the previously developed methods, access to all three classes of aminomethylarenes.     

Synthesis of a platform to access bistramides and their analogues

The platform C14-C40, which can be used to prepare bistramide C and 39-oxobistramide K, was synthesized in 19 steps with an overall yield of 6.2%. Furthermore, the chemoselective reduction of the ketone at C-39 was performed giving an easy access to bistramides A, B, D, K, and L. Finally, the versatility of the synthesis of the C14-C40 fragment can allow the preparation of a large variety of stereoisomers to produce bistramide analogues.     

Synthesis of (+)-vinblastine and its analogues

A synthetic route to vinblastine and its analogues with an ethynyl group, which features a stereoselective coupling of an 11-membered key intermediate with vindoline, is described. Transformations of the alkynyl moiety including a partial reduction as well as a Sonogashira coupling furnished a variety of analogues.     

Glycosidase inhibitors as conformational transition state analogues

A method for estimating the conformational similarity between hexopyranose rings is presented and used to probe the behaviour of various glycosyl hydrolase inhibitors as conformational transition state analogues.     

Rapid synthesis of cyclopropane-dipeptide analogues

The synthesis of cyclopropane-substituted nitrile-dipeptides is reported. The straightforward transformation of the nitrile function into an amide or methylketone function leads to dipeptide analogues of potentially interesting pharmacologic profile.     

A general route to 5,6-seco-hexahydrodibenzopyrans and analogues: first total synthesis of (+)-Machaeridiol B and (+)-Machaeriol B

A general and efficient route for the synthesis of 5,6-seco-hexahydrodibenzopyran and trans-hexahydrodibenzopyran analogues was established, via a highly regio- and stereoselective S_N2′ reaction of arylcyanocuprates to enol silyl ether of α,β-epoxycyclohexanone. It was applied to the first facile total synthesis of (+)-Machaeridiol B and (+)-Machaeriol B.     

Rapid access to acyclic nucleosides via conjugate addition

The synthesis of several acyclic nucleosides 5 and 6, analogs of penciclovir, was achieved by Michael addition as the key step. This reaction worked not only for the protected natural bases but even for the less nucleophilic deaza purine and deaza pyrimidine.     

Stereoselective alkylation of tartrate derivatives. A concise route to (+)-O-methylpiscidic acid and natural analogues

The lithium enolate of (2S,3S,5S,6S)-dimethoxy-2,3-dimethyl-1,4-dioxane-5,6-dithiocarboxylate undergoes stereoselective mono- and/or dialkylations to afford two new stereogenic centers. The alkylation products obtained possessed a cis stereochemistry, which was confirmed by the synthesis of natural 4'-O-methylpiscidic acid dimethyl ester .     

Rapid access to azepine-fused oxetanols from alkoxy-substituted maleimides

[reaction: see text] UV irradiation of alkoxy-substituted N-alkenylmaleimides induces a sequence involving a [5 + 2] cycloaddition followed by a Norrish-Yang cyclization. The resulting highly strained alkylidene oxetanol-fused azepines are formed in good yield and with high diastereoselectivities     

Rapid access to the tricyclic spirotetronic core of abyssomicins

[reaction: see text] Abyssomicins, a novel class of polyketide antibiotics, are characterized by an unprecedented spirotetronic tricyclic subunit in their structure. In this letter, a short synthesis of a suitably functionalized tricyclic precursor of abyssomicins is reported. Key steps of the synthesis are (i) the highly stereoselective Al(III)-tethered Diels-Alder reaction and (ii) the tandem Dieckmann cyclization/TBS trapping of the C9 hydroxyl group followed by a regioselective intramolecular epoxide opening for the assembly of the target tricyclic structure.     

New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation

New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.