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Disorazoles represent a powerful class of highly potent antitubulin natural products isolated from myxobacteria. Herein, we describe a scalable and robust synthesis of (-)-disorazole C

The syntheses of all possible stereoisomers of desfluorinated side products of the potent antihypertensive β-blocker nebivolol are reported. A straightforward approach using a common racemic precursor was employed to obtain the desired optically active building blocks. For one series of compounds, a Sharpless asymmetric epoxidation (SAE) route yielded in a direct fashion the required compounds whereas a Mitsunobu reaction was selected to obtain the other series of compounds. This offers a flexible approach to all desfluoronebivolol side-products in order to fully characterize them.

An access to the dioxabicyclo[3.2.1]octane core of sorangicin A was developed, using a keto lactone formation, a Mukaiyama–Michael reaction and an epoxide opening as the key steps.

Different 4-halo-substituted polyfunctionalized tetra­hydropyrans were easily synthesized by segment-coupling Prins cyclization utilizing magnesium halides. The moderate Lewis acidity allows transformation of substrates bearing acid-labile functional groups. A solvent dependency of the stereochemistry at the C4 carbon was observed.

Efficient synthesis of the key fragments of the complex antibiotics class of sorangicins (Scheme 1) is described. Starting from simple compounds fragments I, II, and IV can be synthesized. For fragment III we chose an approach via L-glucal.

The total synthesis of furano-epothilone D by a convergent route is reported. The key fragments are available on a large scale to provide sufficient material for biological evaluation. The approach involves a palladium-catalyzed coupling that generates a highly functionalized aldehyde which is connected in a stereoselective aldol reaction to yield the framework of furano-epothilone D. Finally, a macrolactonization provides furano-epothilone D.

An efficient synthesis of furano-epothilone C (1) is described by the use of an aldol reaction and a ring-closing metathesis (RCM) for the closure of the macrocyclic ring system. This new type of analog contains a furan ring in the C8-C10 region of the macrocycle. The biology of this new class of epothilone C analog has been studied.

An access to the dioxabicyclo[3.2.1]octane core of sorangicin A was developed, using a keto lactone formation, a Mukaiyama–Michael reaction and an epoxide opening as the key steps.

(R) and (S) of 2-Methy1-3-oxa-5-(tert-butyldiphenylsilyloxyl)methy1pentanoate (4a. 6a) and (R) and (S) of 2-methy1-3-oxa-5-(tert-butyldimethylsilyloxyl)methylpentanoate (4b, 6b) were synthesized by the reaction of the preparative compounds (2a, 2b) with (R) and (S) methy1lactate (3, 4) in the presence of a silver (1) oxide catalyst (Method B). The title compounds are useful for the synthesis of different natural products such as epothilones.

Members of a new class of macrolide—the so-called epothilones (1)—showing a taxol-like biological activity have recently been isolated. A convergent approach to 1 is presented, and the asymmetric syntheses of the three key intermediates 3, 4, and 8 are reported.

Important ring-skeletons, such as hydroazulene 2 , bicyclooctane 4 , or hydrindanone 12 can be easily obtained by Amberlyst 15 (A 15) catalyzed cyclizations of allyl- and propargylsilanes. The total syntheses of (±)-β-pinguisene 5 and (±)-pinguisenol 6 have been achieved by propargylsilane-terminated cyclizations of enone 11 as the key step. Compound 12 was transformed in a straight forward way to provide β-pinguisene 5 and pinguisenol 6 .

The total synthesis of (±)-β-pinguisene 1 has been achieved by a propargylsilane-terminated cyclization of enone 2 as the key step. Compound 3 was transformed in a straight forward way in 10 steps to give β-pinguisene 1 .

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Propargylic silanes of type 2,4,9,11, and 13 undergo smooth cyclization in refluxing benzene and in the presence of AIBN and tributyltin hydride. Ring closure of carbocycles and also of 5- and 6-membered O-heterocyclic rings is achieved in high chemical yields.

Double Michael additions of vinylogous esters of type 1 with crotyl ester generates diastereoselectively bicyclo[2.2.2]octanone 2 with four defined chiral centers via a synclinal transition state. Thexyldimethylsilyl enol ethers of type 5 and 10 undergo smooth cyclization to bicyclo[3.3.1]nonenones 7 and bicylo[3.3.0]octenones 12 by addition of Lewis acids.

Propargylic silanes of type 2,4,9,11, and 13 undergo smooth cyclization in refluxing benzene and in the presence of AIBN and tributyltin hydride. Ring closure of carbocycles and also of 5- and 6-membered O-heterocyclic rings is achieved in high chemical yields.

rac-Sesquiterpenoid AE 1 (rac-1) can be obtained in an 11-step sequence starting from 5-methylresorcinol (2). The key compound 9 is synthesized by the use of a diastereoselective dienone cyclization with the allylic silane 8. Subsequent transformation of 9 leads to rac-1.