Structure Elucidation and Total Synthesis of Kulkenon

Abstract

The impressive biological profile of secondary metabolites isolated from strains of Sorangium cellulosum prompted us to initiate synthetic studies on kulkenon, also isolated from Sorangium cellulosum. The synthesis features a syn-selective vinylogous Kobayashi aldol reaction, recently developed by us, and a ring-closing intramolecular Heck reaction as the pivotal transformations. Comparison of the NMR spectra of the authentic and synthetic material revealed that the proposed configuration had to be revised. A combination of molecular modeling and NOE experiments was used to propose the revised configuration, which was confirmed by a new synthesis.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“… 550 The authors successfully applied this protocol to the total synthesis of kulkenon ( Scheme 209 , bottom) and could revise and firmly assign the stereostructure of this polyketide macrolactone. 551 …”

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

“…In summary, we established a (Z)-selective Buchwald-type coupling reaction as a key step in the synthesis of an advanced fragment of chondrochloren A (1). The required amide 3 can be synthesized in seven steps with a 16% overall yield [16][17][18][19][20], whereas the (Z)-bromide 4 can be generated in a four-step sequence with a 39% overall yield, including a palladiumcatalyzed, stereoselective dehalogenation [21][22][23][24][25].…”

“…Synthesis of (Z)-bromide 4 using a palladium-catalyzed, stereoselective dehalogenation [21][22][23][24]. TBSOTf = tert-butyldimethylsilyl trifluoromethanesulfonate, NCS = N-chlorosuccinimide, 2,6-lutidine = 2,6-dimethylpyridine.…”

“…[21] published an effective way of defunctionalizing dihalogenated double bonds into the corresponding (Z)-monohalogenated derivatives using palladium(II) acetate, triphenylphosphine and tributyltin hydride. Following this procedure, we were able to obtain (Z)-bromide 4 in four steps and an overall yield of 39% [21][22][23][24].…”

Total Synthesis of a Hypothetical Macroketone of Migrastatin

“…As a result of which, the reaction might have proceeded through a comparatively stable transition state A, leading to anti ‐aldol adduct. To verify the anti ‐aldol product, compound 11 was treated with LiBH 4 [19] to afford diol 12 which was converted to bis ‐dinitro benzoyl derivative 13 as a white solid [20] . Thorough analysis of the crystal structure of 13 (diffracted through X‐ray generated from Cu source) confirmed the stereochemistry of the product as (4 S , 5 S , 6 S ), thus leaving no space for stereochemical ambiguity, (Figure 3).…”