The total synthesis of apoptolidin A is described employing an early glycosylation strategy. Strategic disconnections were chosen between C11-C12 (cross-coupling) and C19O-C1 (macrocyclization). The cis-selective glycosylation at C9-OH was achieved with the new SIBA protective group at O2/O3 of the L-glucose residue. Auxiliary substitutents at the 2-position of the 2-deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide. The cross-coupling of the glycosylated northern half with the glycosylated southern half was achieved with CuI-thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20-membered macrolide selectively. H2SiF6 was suitable for the final deprotection of the silyl ethers and the conversion of the C21 methylketal into the hemiketal. The synthetic flexibility of the approach was proven by the synthesis of some glycovariants.

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A convergent total synthesis of the PP2A-inhibitor phoslactomycin A was achieved using a CuTC-mediated coupling of an alkenyl iodide C1-C13 fragment with an C14-C21 alkenyl stannane in the presence of a protected phosphate. Key features for the assembly of the C1-C13 fragment were an asymmetric dihydroxylation, an Evans-Aldol reaction, and a well-balanced protective group strategy. An asymmetric 1,4-addition to cyclohexenone was the key step in the preparation of the C14-C21 fragment.

Stereoselective hydroformylation of methallylic alcohols of types 3 and 4, that employed the substratebound catalyst-directing ortho-diphenylphosphanylbenzoyl (o-DPPB) group, was used as a key step for the construction of bifunctionalized stereotriads, which are central building blocks of polyketide natural products. The required diastereomerically pure syn-and anti-starting methallylic alcohol systems 3 and 4 were obtained either by Cramselective carbonyl reduction, Fra  ter alkylation, or by chelation-controlled carbonyl reduction. Enantiomerically pure stereotriad building blocks were derived from a combination of an Evans aldol addition and subsequent o-DPPB-directed stereoselective hydroformylation (324). A crystal structure analysis for steretriad building block 24 confirmed the relative and absolute configuration of the stereogenic centers. Additionally, it provided evidence for a previously postulated preferred conformation of the catalyst-directing o-DPPB group as well as of the polyketide main chain.

The importance for the right order of functional group introduction and manipulation (good timing) was demonstrated in the course of a total synthesis of phoslactomycin A. The synthetic strategy comprised a Cu(I)-thiophene carboxylate (CuTC, Liebeskind's reagent)-mediated coupling to introduce the Z,Z-diene at the final stage of the synthesis in the presence of a protected phosphate. Key features for the assembly of the C1-C13 fragment were an asymmetric dihydroxylation, an Evans-aldol reaction and an advanced protective group strategy. The C14-C21 fragment was accessible via an asymmetric 1,2-addition to cyclohexenone and a subsequent diastereoselective ketone reduction. One crucial task was the dihydroxylation of the C8-C9 alkene, the introduction of the C6-C7 double bond and the generation of the C25-nitrogen functionality. A second example consisted of the best sequence for the generation of the functional groups in the core part (first phosphorylation, second iodo-olefination, third azide/carbamate conversion). The synthetic solutions from this approach are compared with the already existing contributions in the phoslactomycin area.