Mimicking Halimane Synthases: Monitoring a Cascade of Cyclizations and Rearrangements from Epoxypolyprenes.

We have developed and rationalized a biomimetic transformation mimicking halimane synthases based on a Lewis acid-catalyzed cascade of cyclizations and rearrangements of epoxypolyprenes. Two rings, three stereogenic centers, and a new double bond were generated in a single chemical operation. Based on this cascade transformation, we achieved a unified strategy toward the stereoselective total syntheses of halimene-type terpenoids and analogues as a proof-of-concept study.

Iodine, a Mild Reagent for the Aromatization of Terpenoids.

Efficient procedures based on the use of iodine for the aromatization of a series of terpenoids possessing diene and homoallylic or allylic alcohol functionalities are described. Different examples are reported as a proof-of-concept study. Furthermore, iodine also proved to mediate the dehydrogenation of testosterone.

A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols.

Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule.

Structural diversity from the transannular cyclizations of natural germacrone and epoxy derivatives: a theoretical-experimental study.

Treatment of germacrone (1) with different electrophiles, and of its epoxy derivatives germacrone-4,5-epoxide (2), germacrone-1,10-epoxide (3) and isogermacrone-4,5-epoxide (4) with Brönsted/Lewis acids and Ti(III), gives rise to a great structural diversity. Thus, by using a maximum of two steps, the production of more than 40 compounds corresponding to 14 skeletons is described. Computational calculations rationalizing the structural divergence produced are also described.

First synthesis of (+)-myrrhanol C, an anti-prostate cancer lead.

The first synthesis of (+)-myrrhanol C (1), an antitumor polypodane-type bicyclic triterpene with inhibitory activity against androgen insensitive prostate cancers, is reported herein (IC(50) 10 μmolar). A key step in our convergent synthesis of (+)-myrrhanol C and related analogues is the employment of a microbial stereo- and regioselective late stage C-H oxidation. A low-waste and sustainable process has been developed to prepare (+)-myrrhanol C for further biological studies.

Total synthesis of (+)-seco-C-oleanane via stepwise controlled radical cascade cyclization.

An asymmetric concise total synthesis of the (+)-seco-C-oleanane 1 was accomplished. The successful route to this natural product involves as the key step a stepwise regio- and stereocontrolled catalytic radical polyene cascade cyclization from preoleanatetraene oxide (16), a process mediated by Cp(2)TiCl. The use of this single-electron-transfer complex permits mild cyclization conditions without using unnecessary prefunctionalizations and stops the process at the bicyclic level.

Protecting-group-free synthesis of chokols.

As a result of a combined theoretical and experimental study, we describe a two-step protocol for the preparation of an optically pure, multifunctional, cyclopentanic core shared by a number of natural products. This process is based on a hitherto unreported Ti(III)-mediated diastereoselective cyclization in which the hydroxy-directed template effect played by the Ti(III) species was found to be crucial for the stereoselective outcome of the reaction. The viability of this concept was confirmed with the first protecting-group free synthesis of three enantiopure chokols, namely, chokols K, E, and B.

Practical C-H functionalization of quinones with boronic acids.

A direct functionalization of a variety of quinones with several boronic acids has been developed. This scalable reaction proceeds readily at room temperature in an open flask using inexpensive reagents: catalytic silver(I) nitrate in the presence of a persulfate co-oxidant. The scope with respect to quinones is broad, with a variety of alkyl- and arylboronic acids undergoing efficient cross-coupling.

Weakening C-O bonds: Ti(III), a new reagent for alcohol deoxygenation and carbonyl coupling olefination.

Investigations detailed herein, including density functional theory (DFT) calculations, demonstrate that the formation of either alkoxy- or hydroxy-Ti(III) complexes considerably decreases the energy of activation for C-O bond homolysis. As a consequence of this observation, we described two new synthetic applications of Nugent's reagent in organic chemistry. The first of these applications is an one-step methodology for deoxygenation-reduction of alcohols, including benzylic and allylic alcohols and 1,2-dihydroxy compounds.

Enantioselective total synthesis of the potent anti-inflammatory (+)-myrrhanol A.

The first total synthesis of potent anti-inflammatory polypodanes (+)-myrrhanol A (1), (+)-myrrhanone A (2), (+)-myrrhanone B (3), and (+)-myrrhanol B (4) has been achieved. Key steps in our convergent, highly stereocontrolled route are a Ti(III)-mediated radical cyclization of a chiral monoepoxide to furnish a bicyclic synthon that combines stereospecifically with an acyclic vinyl iodide via an intermolecular B-alkyl Suzuki-Miyaura cross-coupling.

Unusually cyclized triterpenes: occurrence, biosynthesis and chemical synthesis.

The biosynthetic origin of most of triterpenes lies in cascade cyclizations and rearrangements of the acyclic precursors squalene (S) and 2,3-oxidosqualene (OS), processes leading to tetra- and pentacyclic triterpene skeleta. Apart from these, a number of triterpenoid structures derived from cyclization processes, that are different from those leading to tetra- and pentacyclic triterpenes, are also found in Nature. We have defined these processes as unusual cyclizations, and grouped them in three blocks, namely, incomplete cyclizations of the corresponding S-derived precursors, cyclizations of S or OS towards polycyclic triterpenes and subsequent cleavage of the preformed ring systems, and two independent cyclizations of the S- or OS-derived precursor.

First total synthesis of (-)-achilleol B: reassignment of its relative stereochemistry.

The first total synthesis of (-)-achilleol B was achieved using a convergent approach with a longest linear sequence of 14 steps. Three key steps were employed, including an enantioselective Robinson annelation for the construction of the bicyclic moiety. The monocyclic synthon was prepared through a Ti(III)-mediated cylization of a chiral monoepoxide obtained via asymmetric dihydroxylation of geranylacetone.