An alternative stereoselective synthesis of greensporone C

Greensporone C, a new 14-membered resorcylic acid lactone, has been synthesized from inexpensive and commercially available starting materials. This convergent synthesis utilizes Cross metathesis using the Grubbs Hoveyda catalyst, alkylation of 1,3-dithiane and Yamaguchi macrolactonization as key steps.     

Total synthesis and cytotoxic activity of dechlorogreensporones A and D

The first and convergent total syntheses of polyketide natural products dechlorogreensporones A and D have been accomplished in 17 longest linear steps with 2.8% and 5.4% overall yields, respectively, starting from known methyl 2-(2-formyl-3,5-dihydroxyphenyl)acetate and commercially available R-(+)-propylene oxide and 1,2-epoxy-5-hexene. Our synthesis exploited key Mitsunobu esterification and (E)-selective ring-closing metathesis (RCM) to assemble the macrocycles as well as a Jacobsen hydrolytic kinetic resolution to install the stereogenic centers. Both synthetic compounds were found to display significant cytotoxic activity against seven human cancer cell lines with the IC₅₀ ranges of 6.66–17.25?μM.     

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.     

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).     

Total synthesis of (-)-diversifolin

First total synthesis of biologically active germacrane-type sesquiterpene (−)-diversifolin has been achieved. The features of the synthesis involve (i) ring-closing metathesis to give a 10-membered carbocycle, (ii) regioselective Mukaiyama aldol reaction of silyl dienol ether with formaldehyde at the α-position, and (iii) lactone transposition of the fully functionalized 11-oxabicyclo[6.2.1]undecane system.     

A chemoenzymatic and enantioselective total synthesis of the resorcylic acid lactone L-783,290, the trans-isomer of L-783,277

The structure, 5, assigned to the resorcylic acid lactone L-783,290 has been prepared for the first time and in a modular fashion using a Heck reaction to link the readily available fragments 8 and 14. Chemoenzymatic methods were used to prepare the latter fragment, in enantiopure form, from chlorobenzene.     

Stereocontrolled concise synthesis of (±)-halosaline through intramolecular C-H amination

Total synthesis of 2-(2-hydroxyalkyl)-piperidine alkaloid (±)-halosaline is described from 7-octen-4-ol using a Rh-catalyzed chemo- and diastereo-selective intramolecular CH amination of sulfamate ester, ring-closing metathesis, and S_N2 displacement reaction of the six-membered ring sulfamidate as the key steps.     

Total synthesis of mallotophilippen C

The first total synthesis of mallotophilippen C (1), a bioactive chalcone natural product recently isolated from Mallotus philippinensis MUELL. ARG., is described. The synthesis has been accomplished in 11 linear steps from a commercially available material, with an overall yield of 28%.     

Stereoselective total synthesis of cochliomycin A

A convergent and stereoselective synthesis of cochliomycin A, a 14-membered resorcyclic acid lactone, based on chiron approach is described. The key reactions involved olefin cross-metathesis and sodium hydride promoted one-pot intramolecular lactonization. l-Arabinose was used as a chiral pool material for the construction of the key fragment.     

Total synthesis of hyptolide

The total synthesis of hyptolide, a naturally occurring α,β-unsaturated six-membered δ-lactone substituted with a polyoxygenated chain, is described. Sharpless kinetic resolution and opening of two different epoxy alcohols under two different conditions—Swern oxidation conditions and a radical reaction using Cp₂TiCl—fixed the stereocenters at C-9, C-11, and C-12, respectively. Brown’s asymmetric allylation reaction installed the remaining stereocenter at C-6. A RCM protocol was used for construction of the α,β-unsaturated six-membered δ-lactone moiety of the molecule.     

Synthesis of the C1 to C13 tetrahydropyranyl-resorcylate core of paecilomycin B

A d-Glucose derived tetrahydropyran was converted into the C1 to C13 tetrahydropyranyl-resorcylate core of paecilomycin B in seven steps. Key transformations included the synthesis of a diketo-ester dioxinone, which upon thermolysis underwent a retro-hetero-Diels-Alder fragmentation to generate an acyl ketene. This was subsequently trapped by a secondary alcohol affording a triketo-ester, which was efficiently aromatized to produce the advanced resorcylate intermediate.     

First stereoselective total synthesis of Neocosmosin A: a facile approach

First stereoselective concise synthesis of Neocosmosin A, with in vitro binding affinity for human opioid and cannabinoid receptors, has been reported using readily available starting materials such as methylacetoacetate, cyclohexanone, and homoallyl alcohol involved in the key transformations. There are three fragments involved in the synthesis of target molecule, bearing acid functionality, (R)-pent-4-en-2-ol, and Weinreb amide which are synthesized in four, eight, and three steps, respectively. Then the fragments were coupled in four steps to yield the target molecule in an overall yield of 28.6%.     

Pyrrole synthesis using a tandem Grubbs’ carbene-RuCl3 catalytic system

A straightforward pyrrole synthesis from diallylamines is developed by using a tandem catalyst system leading to ring-closing metathesis with the second generation Grubbs’ catalyst (10%) followed by dehydrogenation in the presence of RuCl₃ × H₂O (2%).     

Total synthesis of (±)-hibiscone C

A total synthesis of (±)-hibiscone C, one member of the furanosteroid family of natural products that also includes viridin and wortmannin, is reported. Two new pathways for formation of the key diacyl furan subunit are described.     

Resorcylic acid lactones as new lead structures for kinase inhibition

The naturally occurring resorcylic acid lactones LL-Z1640-2 (1), hypothemycin (2), L-783277 (3), radicicol A (4) and, to a somewhat lesser extent, aigialomycin D (5) have recently emerged as new lead structures for kinase inhibition. Total syntheses have now been reported for all of these natural products, most of which are based on macrocyclization through ester bond formation. However, RCM-based approaches have also been described and a variety of strategies have been pursued to obtain the requisite seco acids or dienes, respectively, as precursors for macrocyclization.     

Total synthesis of diastereomeric marine butenolides possessing a syn-aldol subunit at C10 and C11 and the related C11-ketone

Two diastereomeric marine butenolides, (4S,10R,11R)- and (4S,10S,11S)-4,11-dihydroxy-10-methyldodec-2-en-1,4-olide, possessing a syn-aldol subunit at C10 and C11 have been efficiently synthesized by using a three-module coupling strategy. The enantiomeric syn-aldol modules prepared by the syn-selective aldol reaction of the norephedrine-derived chiral propionates were coupled with the chiral C3-C7 module via 1,3-dithiane bisalkylation. The butenolide ring was then installed via a high-yielding ring-closing metathesis (RCM) reaction. Oxidation of the diastereomeric C11-alcohols furnished the corresponding C11-ketones, which are produced by the same marine microorganism.     

Total synthesis of antifungal gamahonolide A

The first stereoselective total synthesis of gamahonolide A (1) has been accomplished using aminoxylation, Keck allylation, and ring-closing metathesis (RCM) reactions as key steps.     

Parallel synthesis of individual shikimic acid-like molecules using a mixture-operation strategy and ring-closing enyne metathesis

Three new diastereomeric shikimic acid analogues (4-amino-3,5-dihydroxyl-cyclohex-1-en-carboxylic acids, 16) bearing a C-4 amino group were synthesized in parallel by a mixture-operation protocol. Ring-closing enyne metathesis (RCEYM) under ethylene atmosphere was successfully employed to construct the desired carbocycles in high efficiency. The absolute configurations of each final product were confirmed by the 1D and 2D NMR techniques.     

Three-component coupling approach toward the synthesis of a resorcylic acid lactone framework

A resorcylic acid lactone (RAL) framework was constructed based on a three-component coupling approach. The key step was the intermolecular alkylation of a protected cyanohydrin with an aromatic scaffold, and the subsequent carbonylative esterification of the aryl iodide with an alcohol. This sequence allowed the rapid assembly of three components without extra protection/deprotection steps. This synthetic strategy enables the ketone at the 2′ position to be masked as a protected cyanohydrin during the ester formation, thus avoiding an undesired isocoumarin formation. This method should be widely applicable to the synthesis of various types of RAL frameworks.