A mild and convenient method for the preparation of amides from carboxylic acids and isocyanates is described. By using DMAP as a catalyst milder reaction conditions are realised which also allow the conversion of α-chiral isocyanates, as well as α-chiral carboxylic acids without racemisation.

{[2-(Trimethylsilyl)ethoxy]methyl} (SEM)-protected pederic acid 16 was prepared by deriving the stereogenic center at C(7) from mannitol and those at C(2) and C(3) (mycalamide numbering) from trans-2,3-dimethyloxirane. Routes to pederamides involving a late oxygenation at C(7) were explored.Introduction. ± The pederins [1], theopederins [2], mycalamides [3], and onnamides [4] are all amides of type 1 of pederic acid ( (aS,2R,5R,6R)-tetrahydroa-hydroxy-2-methoxy-5,6-dimethyl-4-methylene-2H-pyran-2-acetic acid; 2). In previous syntheses (mycalamides [5] [6], pederin [7 ± 10]) of members of these classes of compounds, the two parts of the target molecules were joined by formation of the amide bond b (cf. Eqn. 1 in Scheme 1). We were interested in a different approach [11], in which bond a is formed, requiring the right-hand building block to carry an isocyanate function. The polarity of this functional group was to be reversed by transformation to a lithiated carbamate, which should then be coupled with a norpederic acid derivative (cf. Eqn. 2). While this approach worked fine with model isocyanates [11], it failed when applied to a more elaborate isocyanate [12] that would have led to a fully functionalized mycalamide. In continuing our efforts, we wanted nevertheless to retain the approach via an isocyanate and considered forming bond b by a decarboxylative coupling of a protected pederic acid to isocyanates (cf. Eqn. 3) [13]. To apply this reaction to a synthesis of pederin or the mycalamides, we needed a reliable route to suitable protected pederic acid derivatives.Several syntheses of pederic acid and derivatives have been reported over the last 25 years [7] [14 ± 19]. Except for two syntheses [18] [19], establishment of the stereogenic center at C(7) (mycalamide numbering) required extra steps, such as oxidation to a ketone and reduction with variable stereoselectivity. Therefore, we opted to derive this stereogenic center from a chiral building block. Second, the previously used [15 ± 17] import of the stereogenic centers at C(2) and C(3) (mycalamide numbering) from enantiomerically pure trans-2,3-dimethyloxirane appeared highly advantageous. This led us to the synthons trans-2,3-dimethyloxirane, 3, and 4 (Scheme 2).We describe in the following a synthesis of the SEM-protected pederic acid 16 along these lines (SEM [2-(trimethylsilyl)ethoxy]methyl).

Synthesis of Pederic Acid and Related Model Studies. -Different investigations and model studies lead to an optimized preparation of the protected pederic acid (I). -(BREITFELDER, S.; SCHUEMACHER, A. C.; ROELLE, T.; KIKUCHI, M.; HOFFMANN*, R. W.; Helv.

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