First enantioselective total synthesis of penicimarin B,aspergillumarins A and B

A convergent enantioselective synthesis of penicimarin B, aspergillumarin A and B has been reported using Brown’s allylation, DeBrabander–Bhattacharjee lactonization and Grubbs cross coupling metathesis. During this synthesis we have standardized the conditions for DeBrabande–Bhattacharjee lactonization to obtain excellent yield (>90%).     

Total synthesis of stagonolide B

Asymmetric total synthesis of nonenolide stagonolide-B has been presented in this Letter. The main highlight of our synthetic strategy is the application of hydroxynitrile lyase (ParsHNL) mediated asymmetric synthesis of cyanohydrin, Sharpless asymmetric dihydroxylation, cross metathesis (CM) reaction, stereoselective Keck allylation reaction and Yamaguchi macrolactonization at a late stage enables us to achieve the synthesis of the target molecule in an efficient way.     

Enantioselective synthesis of attenols A and B

[reaction: see text] Enantioselective synthesis of attenols A and B was accomplished by using diastereoselective hydroboration, Lindlar reduction, and acid-catalyzed acetal formation.     

Stereoselective total synthesis of (+)-boronolide, (+)-anamarine, 8-epi-spicegerolide

A stereoselective total synthesis of the naturally occurring cytotoxic lactones (+)-boronolide, (+)-anamarine, and 8-epi-spicigerolide is described. d-Xylose has been used as a chiral source to construct the four contiguous oxygenated stereogenic centers of target molecules. The diastereoselective allylation was performed using Brown’s protocol and the lactone moiety was prepared by ring closing metathesis.     

Enantioselective synthesis and absolute configurations of aculeatins A and B

The two naturally occuring, bioactive spiroacetals aculeatins A and B have been synthesized for the first time in enantiopure form using an asymmetric allylation as the only chirality source. A further key step was a stereoselective aldol reaction with remote induction. The absolute configurations of the natural products have been established and the previously assigned relative configurations have been corrected.     

Total synthesis of (+)-papulacandin D

A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side-chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side-chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron-rich and sterically hindered aromatic iodide and (2) a Lewis-base catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.     

Total synthesis of aculeatins A and B via a tethered oxa-Michael approach

A stereocontrolled total synthesis of aculeatins A and B has been achieved in eight steps and in 15% overall yield. The key feature of this synthetic approach is the application of a Marouka allylation and tethered intramolecular oxa-Michael reaction to install the required stereocentres on the tetrahydropyran ring.     

Total synthesis of (−)-diospongin A and (+)-cryptofolione via asymmetric aldol reaction

Stereoselective synthesis of two distinctive pyranone skeletons diospongin A and cryptofolione has been described based on an asymmetric aldol reaction starting from Chan’s diene. The synthetic strategy involves the enantioselective Mukaiyama aldol, diastereoselective reduction of δ-hydroxy-β-keto ester, a tandem sequence of deprotection, and intramolecular oxa-Michael reaction to obtain diospongin A and an asymmetric allylation and lactone formation using ring-closing metathesis reaction to obtain cryptofolione.     

Total synthesis of rac-longamide B

rac-Longamide B has been synthesized in six-steps from known starting materials. The synthesis is highlighted by a novel palladium-catalyzed double allylic alkylation of amidopyrroles with 2-butene-1,4-di-tert-butyl dicarbonate.     

Stereoselective total synthesis of cryptopyranmoscatone A1

The first total synthesis of cryptopyranmoscatone A1 isolated from Cryptocarya moschata has been accomplished from 3,4,6-tri-O-acetyl-d-glucal. In addition to the RCM and cross-metathesis (CM) reactions, the synthesis features a highly diastereoselective Brown’s allylation reaction and sets the absolute stereochemistry of the natural product.     

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.     

Total synthesis of stevastelin B3

The total synthesis of stevastelin B3 was achieved using, as a key step, a method developed by us for the synthesis of 2-methyl-1,3-diols by Ti(III)-mediated diastereo- and regioselective opening of trisubstituted 2,3-epoxy alcohols, to carry out the stereoselective construction of its propionate-derived fatty acid segment.     

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.     

Enantioselective synthesis of acyclic allylic esters catalyzed by a palladium/BINAP(S) system

The synthesis of chiral nonracemic acyclic allylic pivalates via the Pd-catalyzed allylic substitution of racemic allylic carbonates is presented. Good to excellent enantioselectivities (up to 90%) were observed in several cases. An extraordinarily high preference for the production of the branched regioisomeric product is seen when starting from 3-buten-2-yl and crotyl substrates. A significant kinetic resolution (k_rel = 38) of the 1,3-dimethylallyl substrate was also observed, leading to the production of esters of both enantiomers of an allylic alcohol with a single enantiomer of catalyst.     

First stereoselective total synthesis of helicascolides A and C

The first total synthesis of helicascolides A and C is reported via acid catalyzed acetonide deprotection followed by intramolecular lactonization in one-pot as the key step.     

Total synthesis of clavosolide A

For the total synthesis of (−)-clavosolide A described herein, a Schmidt glycosidation reaction was used to attach the sugar moiety at an early stage in the synthesis to the 4-hydroxy group of the substituted tetrahydropyran unit of the molecule, which itself was built following a Ti(III)-mediated method developed by us earlier, and at the end, it was the Yamaguchi reaction that was successfully employed for the cyclodimerization of the two halves of the molecule leading to its total synthesis.     

Serendipitous synthesis of 3-hydroxy tetrahydrofurans from tin catalyzed sulfonylation of acyclic 1,2,4-triols

The reaction of syn-1,2,4-triols under sulfonylation conditions catalyzed by Bu₂SnO (5 mol %) results in cyclization and the formation of 3-hydroxy tetrahydrofurans (56-85%) while the anti-1,2,4-triols react to give C1-O-sulfonyl derivatives in good yields (66-83%) and the cyclization product in poor yield (5-12%). A mechanism that justifies these observations is proposed to occur via the tosylation of the primary hydroxyl followed by an intramolecular tin acetal rearrangement to a 1,3-stannylene which then undergoes a 5-exo-tet-cyclization. The difference in rates of cyclization reactivity is due to the energetically more stable tin acetals of syn-1,3-diols compared to those of anti-1,3-diols.