Steve Lanners

Hemisynthesis of two marine cheilanthane sesterterpenes from (−)-sclareol: First enantioselective synthesis of petrosaspongiolide R

The synthesis of two marine sponge metabolites 5 and 8 from naturally occurring (−)-sclareol is described here. The sesterterpenolide (5) is synthetised for the first time, establishing the absolute configuration of this compound. The key intermediate, aldehyde (10), was obtained from (−)-sclareol in good overall yields. The use of Katsumuras Wittig reagent and subsequent photochemical oxidation delivered the sesterterpenolide (8), which was chemoselectively epoxidized on exocyclic terminal olefin using the oxaziridinium salt (14) and transformed in four steps to carboxylic acid (5).

New insights into the reduction of β,δ-diketo-sulfoxides

Abstract New developments in the reduction of β,δ-diketo-sulfoxides, a reaction that affords important key intermediates for total synthesis, are described. We showed without ambiguity using NMR experiments, that the β-carbonyl group is totally enolised. This result is inconsistent with the previous hypothesis, which supposed the other tautomer (enolisation at the δ-position) as the major one. We propose a rationale to explain the side reactions occurring during the reduction of unprotected β,δ-diketo-sulfoxides and showed that judicious protection of the δ-carbonyl group gave all diastereoisomers of β-hydroxy-δ-ketosulfoxides.

FeCl3·6H2O/acetaldehyde, a versatile system for the deprotection of ketals and acetals via a transacetalization process

Mild and efficient catalytic deprotection of ketals/acetals mediated by FeCl3·6H2O/acetaldehyde has been described in this paper. The versatility and high chemoselectivity of the iron(III)/aldehyde system are demonstrated by a large scope of examples. Deprotected ketones/aldehydes are nearly quantitatively isolated after filtration over a pad of silica gel followed by evaporation of volatile by-products.

New Insights into the Synthesis and Biological Activity of the Pamamycin Macrodiolides.

After a brief account of the biological properties of pamamycins, this review highlights the latest developments on the total synthesis and the biosynthesis of these macrodiolides.

Conformation and tautomerism of methoxy-substituted 4-phenyl-4-thiazoline-2-thiones: a combined crystallographic and ab initio investigation.

4-Phenyl-4-thiazoline-2-thiol is an active pharmaceutical compound, one of whose activities is as a human indolenamine dioxygenase inhibitor. It has been shown recently that in both the solid state and the gas phase, the thiazolinethione tautomer should be preferred. As part of both research on this lead compound and a medicinal chemistry program, a series of substituted arylthiazolinethiones have been synthesized. The molecular conformations and tautomerism of 4-(2-methoxyphenyl)-4-thiazoline-2-thione and 4-(4-methoxyphenyl)-4-thiazoline-2-thione, both C10H9NOS2, are reported and compared with the geometry deduced from ab initio calculations [PBE/6-311G(d,p)]. Both the crystal structure analyses and the calculations establish the thione tautomer for the two substituted arylthiazolinethiones. In the crystal structure of the 2-methoxyphenyl regioisomer, the thiazolinethione unit was disordered over two conformations. Both isomers exhibit similar hydrogen-bond patterns [R2(2)(8) motif] and form dimers. The crystal packing is further reinforced by short S...S interactions in the 2-methoxyphenyl isomer. The conformations of the two regioisomers correspond to stable geometries calculated from an ab initio energy-relaxed scan.

Solid-State-Trapped Reactive Ammonium Carbamate Self- Derivative Salts of Prolinamide

Single crystals for two polymorphs of the ammonium carbamate self-derivative salt of prolinamide have been successfully obtained and characterized. Decarbonation of the carbamate salts was monitored by calorimetry, confirming stabilization of the reactive carbonated adducts in the solid state. Sublimation of the salts afforded crystals of prolinamide, leading to the first crystal structure of this otherwise common molecule. Reactivity of the ammonium carbamate self-derivative salt is further illustrated by the observation of a series of derived products, including dehydroprolinamide, a methylene-bridged prolinamide, and a bicyclic derivative. Crystal structures of these products display distinct amidic and/or non-amidic hydrogen bonding. This study emphasizes the reactivity of carbonated amines stabilized in the solid and opens perspectives for a systematic study of (solid-state) reactions involving these trapped reactive species.

First Total Synthesis of Pamamycin-621D

Pamamycin-621D, a member of a large family of macrodiolides with antimycobacterial properties, has been synthesized and fully characterized for the first time. A convergent and flexible strategy based on a key aldol coupling delivered this less abundant pamamycin congener. Furthermore, the synthesis of a new unsaturated precursor using cross-metathesis was developed in order to suppress regioselectivity issues in the aldol coupling step.

Synthesis of 4- and 5-arylthiazolinethiones as inhibitors of indoleamine 2,3-dioxygenase

Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic routes had to be adapted and optimized to yield the desired substituted 4- and 5-arylthiazolinethiones. Their biological evaluation shows that 5-aryl regioisomers are systematically less potent than the corresponding 4-aryl analogs. Substitution on the phenyl ring does not significantly increase inhibition potency, except for 4-Br and 4-Cl derivatives.