Total synthesis of (−)-haploscleridamine

Asymmetric total synthesis of the imidazole containing β-carboline natural product, haploscleridamine, from histidine is described. Key to the successful assembly of this alkaloid is a ring-closing metathesis reaction of an imidazole derived allylic alcohol to construct a 3-piperidinone. Application of the Buchwald-modification of the classical Fischer indolization and deprotection of the N-tosyl moiety delivered haploscleridamine.     

The stereoselective total synthesis of PF1163A

A stereoselective total synthesis of 13-membered macrocycle PF1163A, an antifungal agent, has been accomplished for the first time starting from d-xylose. This approach involves a diastereoselective allylation of lactal ether,^3a reductive ring opening of tetrahydrofuran ring,^3b asymmetric methylation reaction, Yamaguchi esterification, and ring closing metathesis as key steps.     

Enantiospecific total synthesis of (−)-crotanecine

Crotanecine is the necine base component of a number of pyrrolizidine alkaloids. This necine subunit is an amino triol bearing a primary allylic alcohol characterized by an all-cis relationship of its stereocenters. The synthesis of crotanecine has been accomplished using simple yet versatile ring construction approach using ribose as chiral starting point.     

Stereoselective Total Synthesis of Botryolide E

The stereoselective total synthesis of the naturally occurring γ‐lactone derivative botryolide E ( 1 ) was accomplished with acetaldehyde as the starting material (Scheme 2). The asymmetric allyl boration, asymmetric dihydroxylation, chelation‐mediated diastereoselective vinylation, and ring‐closing metathesis reaction are the key steps. The method can conveniently be utilized for the preparation of other related γ‐lactone derivatives.     

Total synthesis of heliannuol B, an allelochemical from Helianthus annuus

A total synthesis of the allelochemical heliannuol B 1 is described employing ring closing metathesis to generate the central benzoxepane ring system.     

Total synthesis of topsentolide B2

A stereoselective total synthesis of topsentolide B₂, a selective cytotoxic oxylipin against SK-OV-3 and SK-MEL-2 cancer cell lines has been achieved based on asymmetric dihydroxylation, Roush allylation, and ring closing metathesis (RCM) reactions. The synthesis is completed in 11 steps and 2.1% overall yield.     

A concise and stereoselective total synthesis of L-783,290

A stereoselective total synthesis of L-783,290 has been achieved involving Alder–Rickert reaction, ring closing metathesis, and chemoselective oxidation as key steps. This approach has successfully demonstrated a linear sequence of reactions, which are highly stereoselective for the construction of the resorcylic acid unit.     

Total Synthesis of (±)‐Infuscol A and (±)‐Cuprenenol

Abstract

Total synthesis of the nonaromatic cuparenoid sesquiterpenes (±)‐infuscol A and cuprenenol, and (±)‐infuscol B and neocuprenenol isolated from the Japanese liverwort Jungermannia infusca has been accomplished. Two ring‐closing metathesis reaction based strategies have been developed for the generation of the key intermediate of the sequence.     

Asymmetric synthesis of cyclic β-hydroxyallylsilanes via sequential allyltitanation-ring closing metathesis

Highly enantioenriched cyclic β-hydroxyallylsilanes have been prepared via enantioselective allylation of unsaturated aldehydes using a chiral allyltitanium reagent, followed by a ring-closing metathesis. Functionalized rings of various sizes have been synthesized and the electronic effect of the silicon group in the RCM reaction has been studied. The resulting cyclic β-hydroxyallylsilanes reacted stereoselectively with a variety of electrophilic reagents. A first application of this method to the synthesis of a highly functionalized dihydropyrane is reported.     

Enantioselective synthesis of (+)-anatoxin-a via enyne metathesis

A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed by a series of nine chemical operations and in 27% overall yield from commercially available d-methyl pyroglutamate (12). The strategy featured the application of a new protocol for the diastereoselective synthesis of cis-2,5-disubstituted pyrrolidines bearing unsaturated side chains and an intramolecular enyne metathesis to provide the bridged bicyclic framework of 1. Thus, d-methyl pyroglutamate (12) was converted in five steps to 32, which underwent facile enyne metathesis to deliver the bicyclic diene 33. Selective oxidative cleavage of the less substituted carbon-carbon double bond in 33 followed by deprotection furnished (+)-anatoxin-a (1).     

Total synthesis of greensporone C

The first total synthesis of greensporone C, a cytotoxic 14-membered resorcylic acid lactone, has been accomplished via a longest linear sequence of 16 steps in 3.3% overall yield. The key features of the synthesis include Mitsunobu esterification and ring-closing metathesis to construct the macrocycle and establish the (E)-olefin geometry, respectively. Our synthesis also confirmed the absolute stereochemistry of the natural product.     

Diastereoselective synthesis of highly substituted polycyclic scaffolds via a one-pot four-step tandem catalytic process

A rapid and diastereoselective synthesis of highly substituted aminobicyclo[4.3.0]nonanes and bicyclo[4.4.0]decanes from alkyne derived allylic alcohols has been developed using a one-pot multi-bond forming tandem catalytic process. Overman rearrangement of the allylic trichloroacetimidates was followed by a ring closing enyne metathesis/cross metathesis sequence of reactions, in which both steps were catalysed by Grubbs second generation catalyst. The resulting exo-diene was then subjected to a hydrogen bonding directed Diels–Alder reaction forming an endo-adduct as a single diastereomer. Variation of the cross metathesis partner and dienophile allowed examination of the scope of this one-pot process and the preparation of a diverse series of highly substituted polycyclic scaffolds.     

Stereoselective synthesis of tarchonanthuslactone via the Prins cyclisation

The stereoselective total synthesis of tarchonanthuslactone, a polyketide natural product, has been achieved. The synthesis exploits the high stereochemical control in the Prins cyclisation along with ring closing metathesis (RCM) as a key step.     

Total synthesis of brevenal

The convergent total synthesis of brevenal, a non-toxic brevetoxin antagonist, has been achieved. The ABC ring segment and the E ring precursor were connected by the intramolecular allylation followed by ring-closing metathesis to furnish the pentacyclic ether compound. An alternative route to the key synthetic intermediate, a pentacyclic ether core, was also examined. The right- and left-hand side chains were introduced by Wittig and Horner-Wadsworth-Emmons reactions, respectively, to furnish brevenal (1).     

Stereoselective synthesis of advanced intermediates en route to Taxuspine U and X: a study of macrocyclization via ring closing metathesis to highly constrained twelve-membered rings

The stereoselective synthesis of an advanced intermediate of Taxuspine U and X has been accomplished using a ring closing metathesis strategy. The feasibility of ring closing metathesis in synthesizing highly constrained and functionalized macrocycles has been demonstrated provided the appropriate substrate structure and substitution pattern are chosen.     

Stereoselective Total Synthesis of Rugulactone

The stereoselective synthesis of the naturally occurring dihydropyranone rugulactone has been accomplished starting from 3‐phenylpropan‐1‐ol employing Maruoka allylation and ring‐closing metathesis as the key steps.     

Stereoselective Total Synthesis of Multiplolide A and of a Diastereoisomer

A stereoselective total synthesis of multiplolide A ( 1 ) and of its diastereoisomer 2 was described from easily accessible starting materials (Schemes 2–4). The synthetic strategy involves a Jacobsen resolution, Sharpless epoxidation, Swern oxidation, Yamaguchi reaction, and ring‐closing metathesis (RCM).     

Total synthesis of the tricyclic humulanolide wilfolide B

The first total synthesis of tricyclic humulanolide wilfolide B was achieved. The synthetic strategy involved: i) radical cyclization with samarium(II) iodide to construct the bicyclic lactone from an acyclic compound, and ii) ring-closing metathesis to build the eight-membered ring by connecting two side chains, thus completing the tricyclic framework.     

A concise synthesis of β-lactam-sulfonamide hybrids

Using ring closing metathesis (RCM) as the key operation, a rapid access to β-lactams fused to a sultam moiety of variable ring size was developed from low cost, commercially available starting materials. An efficient RCM of 4-vinyl-azetidin-2-ones to give 1-aza-bicyclo[4.2.0]oct-4-en-8-ones is also reported.