Stereoselective total synthesis of cytotoxic sporiolide A

A simple and highly efficient stereoselective total synthesis of cytotoxic agent sporiolide A has been achieved starting from d-mannitol; the strategy of synthesis utilizes stereoselective zinc-mediated allylation, aldol coupling and ring-closing metathesis as key steps.     

Stereoselective total synthesis of sporiolide B and attempted synthesis of sporiolide A

A simple and efficient stereoselective total synthesis of sporiolide B and attempted synthesis of sporiolide A, from epichlorohydrin, using asymmetric synthetic approach is reported. The key reactions involved are Sharpless epoxidation, Jacobsen reaction, syn-allylation, Yamaguchi esterification, and Grubbs ring-closing metatheses reaction to result in the macrocyclic ring system.     

The first total synthesis of sporiolide A

The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound.     

The first stereoselective total synthesis of the Z-isomer of cytospolide E

A convergent and highly stereoselective total synthesis of the Z-isomer of cytospolide E has been achieved via Evan’s aldol reaction, Sharpless kinetic resolution and RCM cyclisation.     

Formal synthesis of tirandamycin B

A formal synthesis of tirandamycin B is described. The key intermediate is synthesized by Marshall allenyl zinc method, litiofuran coupling, and Achmatowicz reaction to construct the bicyclic core of tirandamycin B.     

Formal total synthesis of hemibrevetoxin B by a convergent strategy

Concise construction of the trans-fused 7/7/6/6 tetracyclic ether part of hemibrevetoxin B (1) was achieved by a convergent strategy based on coupling reaction of an acyl anion equivalent, reductive cyclization of an α,ε-dihydroxyketone, and introduction of a methyl group at the central ring junction by the Nicolaou method. The resultant tetracyclic ether was transformed into the known intermediate, which was already converted to 1 by the Yamamoto group, thereby completing the formal total synthesis of 1.     

Studies toward asymmetric synthesis of leiodelide A

An enantioselective route for oxazoline 4, a key fragment toward the asymmetric synthesis of leiodelide A, is described. We synthesized northern subunit 6 through a Julia–Lythgoe olefination and subsequent Sharpless asymmetric dihydroxylation. Moreover, a highly diastereoselective method using well-established Evans’ asymmetric aldol condensation was developed for preparation of southern fragment 5. The additional feature of this synthetic route is the formation of oxazoline 4 through DAST-promoted cyclization of the amidation product from subunits 5 and 6.     

The first total synthesis of (±)-laurokamurene B

The first total synthesis of the rearranged aromatic sesquiterpene (±)-laurokamurene B, isolated from the Chinese red alga Laurencia okamurai Yamada, has been accomplished, confirming the structure of the natural product. A combination of Ireland-Claisen rearrangement and ring-closing metathesis was employed as key reactions.     

The first synthesis of ent-agelasine F

Agelasine F has previously been isolated from marine sponges (Agelas sp.) and has been associated with various bioactivities including inhibitory activity on Mycobacterium tuberculosis. No total synthesis of this natural product has been reported. ent-Agelasine F has now been synthesized for the first time, starting from (R)-pulegone. The synthesis is considerably more efficient than a previously reported route to rac-agelasine F. ent-Agelasine F is found to exhibit antimicrobial activity.     

The first total synthesis of prianosin B

The first asymmetric total synthesis of prianosin B (1) is described. Formation of the 16,17-dehydropyrroloiminoquinone skeleton from the pyrroloiminoquinone unit is a key step in this synthesis. Thus, the detosylation and dehydrogenation reactions of the pyrroloiminoquinone unit are caused by the presence of a catalytic amount of NaN₃.     

The first total synthesis of (±)-zenkequinone B

The first total synthesis of tetrahydrobenzo[a]anthraquinone natural product (±)-zenkequinone B (1) is reported. The key step involves the TiCl₄-promoted intramolecular cyclization of 4-aryl-2-hydroxybutanal diethyl acetal 4 to give compound 3. The total synthesis of (±)-zenekequinone B (1) has been accomplished in five steps from readily available 2-(chloromethyl)-9,10-dimethoxyanthracene (5) in 40.3% overall yield.     

Synthesis of aspergillide A from a synthetic intermediate of aspergillide B

The first synthesis of aspergillide A, a cytotoxin produced by a marine-derived fungus, has been achieved from a synthetic intermediate of aspergillide B by using a proline-mediated epimerization of a 2,6-trans-substituted tetrahydropyran-2-acetaldehyde intermediate into the corresponding cis-isomer via a retro-oxy-Michael/oxy-Michael sequence as the key transformation.     

The first total synthesis of Cicerfuran utilizing a one-pot synthesis of hydroxylated benzofurans

A simple one-pot procedure was elaborated for the preparation of hydroxylated benzofurans from halogenated phenols and was successfully applied to the first total synthesis of Cicerfuran, a natural defence agent of wild chickpea.     

Total synthesis of modified pentapeptide,caldoramide

Total synthesis of modified pentapeptide, caldoramide, a cytotoxic linear pentapeptide from the marine cyanobacterium Caldora penicillate is described. Notable features of the route include the efficient preparation of three key fragments and final assembly to the natural product via sequential amide couplings. The spectral data of the synthetic compound was found to be in comparison with that of the isolated natural product.     

Asymmetric total synthesis of phomonol

An efficient asymmetric total synthesis of phomonol 1 is presented, starting from (S)-1,2-epoxypentane. The synthesis features Sharpless asymmetric dihydroxylation (AD), diastereoselective reductive etherification and Wacker oxidation as key steps.     

First total synthesis of the antifungal antibiotic thiobutacin

The first total synthesis of thiobutacin, a butanoic acid with antifungal activity recently isolated from the culture broth of a soil actinomycete, Lechevalieria aerocolonigenes strain VK-A9, is described. The five-step procedure involves readily available and cheap starting materials and can easily be transposed to the large scale. Fungal growth inhibition of thiobutacin is mediated by the pH of the growth medium. Maximum inhibitory activity was obtained between pH 6 and 7.     

The first total synthesis of usabamycins a and C

The first total synthesis of usabamycins A and C from inexpensive and readily available amino acids – homoalanine and glycine and featuring a stereoselective Ireland-Claisen rearrangement as well as a novel 7-membered ring formation reaction is described.     

A total synthesis of spiruchostatin A

We achieved the total synthesis of the histone deacetylase inhibitor spiruchostatin A, as the prelude to the preparation of a combinatorial library of its analogues. Two key reactions were an asymmetric acetate aldol reaction using a Zr-enolate and macrolactonization using the Shiina method.     

Recent advances of desymmetrization protocol applied in natural product total synthesis

Desymmetrization synthesis strategy has simplified and improved the efficiency of synthesis, which attracted great attention in the past few decades. Since the strategy has been developed rapidly and got a wide range of applications in natural product total synthesis, the rules are urgent to be summarized. In this Letter, the recent developments of desymmetrization protocol in natural product total synthesis were summarized.