Patulolides

This method was successfully used in a concise catalytic enantioselective total synthesis of (+)-patulolide C by serving as a key asymmetric C—O bond formation step (Scheme 5.33)." ... 

There are also known macrolides with a 12-membered lactone ring, which received the name of patulolides, as well as those with a 16-membered lactone ring, which are called isenamycins. Today, there are about 100 compounds that make up this group of macrolide antibiotics, and they are generally produced by streptomycetes. 

A more recent chemoenzymatic synthesis of the related (R)-patulolide A has also been published A. Sharma, S. Sankaranarayanan and S. Chattopadhyay, J. Org. Chem., 1996,61, 1814. 

Zwanenburg and coworkers [38] modified the Yamaguchi procedure in the synthesis of the 12-membered macrolide patulolide C 61). Mixed 2,6-chloro-benzoic anhydride, instead of mixed 2,4,6-trichlorobenzoic anhydride, was used. 

It was also shown in the enantioselective synthesis of the macrolide patulolide that the anion of methyl p-tolyl sulfoxide was more reactive towards the imidazolide, prepared from the hemi ethyl sebacate, than the ester group (eq 7). 

Thijs, L., Egenberger, D. M., Zwanenburg, B. An enantioselective total synthesis of the macrolide patulolide C. Tetrahedron Lett. 1989, 30, 2153-2156. 

Sekiguchi, J., Kuroda, H., Yamada, Y., and Okada, H. (1985). Structure of patulolide A, a new macrolide from Penicillium urticae mutants. Tetrahedron Lett. 26, 2341 -2342. 

Ring contraction in more complicated ring systems still appears to be a viable reaction path. Thus the irradiation of 457 yields 458 while 459 also undergoes ring contraction . An approach to the paddlane skeleton has also be described using the double contraction to the diketone 460 and brought about by irradiation of 461. Other examples of ring contraction have been used as key steps in the synthesis of (-)-aspicilin, patulolide and (-)-oxetanocin (Scheme 21) ". ... 

The antibiotic ff-(+)-patulolide (17), first isolated in 1985 from the culture broth of Penicillium urticae mutant S11R59, was obtained from hydrox-... 

Thomas and Hoegenauer achieved aliphatic 1,8-stereocontrol in the S5mthesis of racemic patulolide C 157 and epipatulolide C 158 via [2,3]-Wittig rearrangement of bisallylethers such as 160. ° The stereochemistry of the racemic product was confirmed by completion of the synthesis and comparison with natural epipatulolide C. Thomas reported several other... 

Risi and Burke [29, 30] synthesized (+)-patulolide C, which is a macrocyhc compound isolated from a Penicillium urticae mutant via an asymmetric sequential hydroformylation-(intramolecular Wittig olefination) reaction applying... 

Bestmann s ylide 0=C=C=PPh3 as a Cj buUding block (Scheme S.ldO). ) The required substrate was derived by the rhodium-catalyzed addition of acetic acid to a terminal alkyne. For the asymmetric rhodium-catalyzed hydroformylation at 10.3 bar, Landis s (S,S,S)-BDP was used as ligand. After hydroformylation and ring closure, the protecting 0-acetyl group was removed by the effect of an enzyme to finally produce (+)-patulolide C in an overall yield of 49%. 

The lanthanide (or yttrium)-lithium heterobimetallic complexes, LnLB was found to promote catalytic asymmetric cyano-ethoxycarbonylation reaction and cyano-phosphorylation reaction of aldehydes [164]. In these reactions, H2O, BuLi, and Ar3P(0) (Ar = 2,6-dimethoxyphenyl) were essential to achieve high enantioselectivity as well as good reactivity (Scheme 13.53). A total synthesis of patulolide C was achieved using the catalytic asymmetric cyano-ethoxycarbonylation reaction... 

Most of the pharmacologically active macrolides have highly substituted structures as can be seen from the examples shown earlier. However, complexity of the structure is not essential for biological activity and relatively simple macroHdes such as aspergillides 24 and patulolides 25 (Figure 6.10) possess interesting properties that make them worth studying. 

Patulolide C 25c (Scheme 6.10), a 12-membered macrolactone, was first isolated by Yamada et al. [73] in 1985 from the culture filtrate of PeniciUium urticae S11R59 mutant, along with its congeners patulolides A 25a and B 25b exhibiting both... 

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