Total synthesis of amphidinolide J

The marine natural product amphidinolide J has been synthesized according to a convergent strategy. The key steps of this synthesis include a B-alkyl Suzuki-Miyaura coupling and the addition of an alkynyllithium reagent to a Weinreb amide to build the C4-C5 and C12-C13 bonds, respectively, and a Yamaguchi macrolactonization.     

Total synthesis of cortistatins A and J

This paper describes the details of our synthetic studies on the marine steroidal alkaloids cortistatins A and J. The key features of our strategy include (i) an efficient Knoevenagel/electrocyclic strategy to couple the diketone and the CD-ring fragment, (ii) a chemoselective radical cyclization to construct the oxabicyclo[3.2.1]octene B-ring system, (iii) a highly stereocontrolled installation of the isoquinoline unit, and (iv) a late-stage functionalization of the A-ring.     

Total synthesis of (+)-cyanthiwigin U

A concise total synthesis of the tricyclic terpene cyanthiwigin U has been accomplished in 12 steps and 17% overall yield. The key step of the synthesis is a two-directional tandem metathesis reaction that forms the cyclohepta[e]indene core from a readily available bicyclo[2.2.2]octene.     

Total synthesis and correct absolute configuration of malyngamide U

The enantioselective synthesis of the previously proposed structure of malyngamide U (1) was accomplished in 18 steps from (S)-(+)-carvone. The key steps involved a hydroxymethylation of (S)-(+)-carvone and an asymmetric Henry reaction of aldehyde (+)-5, as well as condensation with the acid 3. The 1H and 13C NMR data of the synthetic compound 1 were not consistent with the data of the reported malyngamide U. The C-2' epimer of compound 1 was therefore synthesized by a similar reaction sequence. While the NMR data of C-2' epimer 23 were in full agreement with those of the reported product, the discrepancy in the specific rotation data suggested the correct structure of malyngamide U should be structure 2, in which the absolute configuration of the amine part was enantiomeric with that in compound 23. Then the correct absolute configuration of revised malyngamide U (2) was confirmed by the similar synthesis from (R)-(-)-carvone.     

Total synthesis of (+/-)-bipinnatin J

[reaction: see text]. The total synthesis of (+/-)-bipinnatin J was achieved through a concise route that features the use of a silver ion promoted S(N)1-type gamma-alkylation of a siloxyfuran and a diastereoselective Cr(II)-mediated macrocyclization to provide bipinnatin J (1), wherein the remote furanone stereocenter at C10 induced the relative stereochemistry of the two additional stereocenters.     

Total synthesis of the proposed structure of briarellin J

The total synthesis of the originally proposed structure of briarellin J is reported in 15 steps from a known compound and in 23 steps from readily available materials. Key reactions include an exo-selective intramolecular Diels-Alder and a substrate-controlled hydroboration. Discrepancies in the spectroscopic data of the synthetic and natural material led to a revision of the assigned structure.     

Total synthesis of endiandric acid J and beilcyclone A from cyclooctatetraene

The endiandric acids are classic targets in natural product synthesis. The spectacular 8π/6π-electrocylisation/intramolecular Diels–Alder (8π/6π/IMDA) reaction cascade at the heart of their biosynthesis has inspired practitioners and students of pericyclic chemistry for nearly forty years. All previous synthetic approaches have sought to prepare a linear tetraene and thereby initiate the cascade. In this communication we demonstrate the use of cyclooctatetraene to rapidly intercept the 8π/6π/IMDA cascade at the cyclooctatriene stage. Endiandric acid J and beilcyclone A are prepared for the first time in six and five steps, respectively. The strategy features a tactical overall anti-vicinal difunctionalisation of cyclooctatetraene through S_N2′ alkylation of cyclooctatetraene oxide followed by an intriguing tandem Claisen rearrangement/6π-electrocyclisation from the corresponding vinyl ether. This rapidly constructs an advanced bicyclo[4.2.0]octadiene aldehyde intermediate. Olefinations and intramolecular Diels–Alder cycloadditions complete the syntheses. This establishes a short and efficient new path to the endiandric acid natural products. DFT modelling predicts thermal racemisation of bicyclo[4.2.0]octadiene intermediates, dashing hopes of enantioselective synthesis.

A new strategy to the endiandric acid natural products is demonstrated by intercepting the 8π/6π/IMDA pericyclic cascade through a tactical anti-vicinal difunctionalisation of cyclooctatetraene.     

Total synthesis of artochamins F, H, I, and J through cascade reactions

A concise and efficient cascade-based total synthesis of artochamins F, H, I, and J is described. The potential biogenetic connection between artochamin F, or a derivative thereof, and artochamins H, I, and J, through an unusual formal [2+2] cycloaddition process, was shown to be feasible. An alternative mechanism for this transformation is also proposed.     

Total synthesis of granulodione

In this paper, we report the total synthesis of a sesquiterpene, granulodione, having a 15-norilludane skeleton. The coupling of two fragments 3 and 4 via aldol condensation, followed by Saegusa oxidation, SmI₂-mediated cyclization, and oxidation enabled expeditious and efficient synthesis of granulodione.     

Total synthesis of mangiferaelactone

Herein we document the first total synthesis of mangiferaelactone and thus establish its absolute configuration. The central nonenolide ring was constructed using ring closing metathesis and Yamaguchi esterification. The key alcohol fragment was synthesized by the Bernet–Vasella fragmentation of C-ribofuranoside.     

Total synthesis of neosurugatoxin

Total synthesis of neosurugatoxin, having a strong affinity for nicotinic receptors, is described.     

Total synthesis of lespedezavirgatol

Lespedezavirgatol, a novel 2-phenylbenzofuran compound which was isolated from Lespedeza virgata, was firstly synthesized from pyrogallic acid and 3,4-dimethoxyphenol as starting materials with 8 steps. The key steps for the total synthesis were the selective iodination at 3-position of 1,2-dimethoxy-4-methoxymethoxybenzene and the Sonogashira cross-coupling reaction between 4-iodo-2-methoxybenzene-1,3-diol and 2-ethynyl-3,4-dimethoxy-1-(methoxy-methoxy)-benzene.     

Total synthesis of brevenal

This Article describes the total synthesis of the marine ladder toxin brevenal utilizing a convergent synthetic strategy. Critical to the success of this work was the use of olefinic-ester cyclization reactions and the utilization of glycal epoxides as precursors to C-C and C-H bonds.