Macrodiolides synthesis

Wakamatsu, T, Nakamura, H, Naka, E, Ban, Y, Synthetic studies on antibiotic macrodiolide synthesis of the A-segment of elaiophylin. Tetrahedron Lett., 21, 3895-3898, 1986. 

Metz P (2005) Synthetic Studies on the Pamamycin Macrodiolides. 244 215-249 Metzner P (1999) Thiocarhonyl Compounds as Specific Tools for Organic Synthesis. 204 127-181... 

Keywords Pamamycins Macrodiolides Antibiotics Synthesis Hydroxy acids... 

With both building blocks 103 and 109 in hand, the total synthesis of lb was completed as shown in Scheme 17. Coupling of acid 103 and alcohol 109 under Yamaguchi conditions to give ester 110 and subsequent desilylation followed by chemoselective oxidation provided hydroxy acid 111. Lactonization of the 2-thiopyridyl ester derived from 111 in the presence of cupric bromide produced the macrodiolide 112 in 62% yield, which was finally converted to pamamycin-607 (lb) via one-pot azide reduction/double reductive AT-methylation. In summary, 36 steps were necessary to accomplish the synthesis of lb from alcohols 88 and 104, sulfone 91, ketone 93, and iodide rac-97. 

Mulzer and Berger used the Midland reduction en route to the total synthesis of the boron-containing macrodiolide antibiotic tartrolon B (90), which acts... 

Su et al. [53] used allylsilanes having C-centered chirality and a distannoxane transesterification catalyst [54] in a sequence of transesterification reactions to rapidly assemble a set of stereochemically diverse macrodiolides reminiscent of polyketide-derivative natural products. Figure 15.20 summarizes the synthesis of stereochemically well defined 14- and 16-member macrodiolides 20.4 and 20.5, resembling known polyketide-derived natural products, from hydroxyl esters 20.2 and 20.3. The feasibility of cyclodimeriztion was studied using different solvents and variable concentrations. Reactions were affected by the choice of the solvent. 

The synthesis was performed according to a two-directional synthesis strategy [219] since the macrodiolide core part in the target compound has C2-symmetry. The synthetic pathway is... 

Swinholide A. The swinholides are a series of complex macrodiolides isolated from the marine sponge Theonella Swinhoei, which display potent cytotoxicity against a range of human tumour cell lines. Swinholide A (71) provided an excellent opportunity to showcase the synthetic utility of a range of aldol reactions. For its total synthesis by our group in 1994 [50] the fully protected preswinholide A 72 was considered to be an essential late-stage intermediate, which appeared accessible via two directed aldol reactions of a suitable butanone equivalent with aldehydes 73 and 74 (Scheme 9-24). 

The vinyl-1,4-dioxane rearrangement using the Ireland variation has been used for the synthesis of macrodiolide and macrotriolidc ionophores with C2 and C3 symmetry324. 

Some trichothecenes, a group of mycotoxins, have macrodiolide or macrotri-olide skeletons. Trichothecenes inhibited protein synthesis by binding to the ribosomal peptidyltransferase site [141]. Roritoxins (roritoxin A, 113) are 16-membered ring macrodiolides isolated from Myrothecium roridum [142]. Verru-carin A (114) is an 18-membered ring macrotriolide produced by Myrothecium spp. [143]. 

Total synthesis of oxacyclic macrodiolide natural products 05CRV4348. 

The elaiophylin synthesis is based on an aldol reaction of the ethyl ketone 278 and the dialdehydic 16-membered-ring macrodiolide 282, which were prepared from D-glucose and 2-deoxy-t-fucose. In this synthesis, diethylisopropylsilyl (DEIPS) and isopropyldimethylsilyl (DMIPS) groups were developed and used as effective 0-protecting groups. 

Hillis [1985] (Scheme 28) [51] and Bestmann [1987] (Scheme 28) [52] reported the total synthesis of a 14-membered-ring macrodiolide, (/ ,/ )-(—)-graha-mimycin Aj (293) by using 290 and 291, respectively, as starting materials. In the Bestmann synthesis, the ester 292, which was prepared from the alcohol and ketenylidenetriphenylphosphorane, was used for cyclization. 

The total synthesis of the 16-membered macrodiolide elaiophilin has been accomplished by a route which involved as a key step the reaction of a boron enolate of (47), derived from glucose (numbers... 

Application of this methodology to the two-directional conversion of the Cj-symmetric diol 192 with ethyl vinyl ketone yielded the mono oxa-Michael adduct of the intermediate double CM product with a high diastereomeric ratio (Scheme 2.68) [39ej. The depicted major isomer 193 was then used for a concise total synthesis of the molluscicidal macrodiolide cyanoHde A. 

A full account has been given of the synthesis of the macrodiolide elaiophylin (see Vol.20, p.264).30... 

Kang, E.J. and Lee, E. (2005) Total synthesis of oxacydic macrodiolide natural products. Chem. Reu., 105, 4348-4378. 

Sch 351448 (72), isolated from Micromonospora, is a novel activator of low-density lipoprotein receptor (LDL-R) promoter with an IC50 of 25 nM, which features a 28-membered macrodiolide consisting of two identical hydroxy carboxylic acid units. In its synthesis, intramolecular olefin metathesis of 70 mediated by [Ru]-II proceeded smoothly, and the macrodiolide was obtained after a hydro-genation/hydrogenolysis sequence (Scheme 5.16) [39]. Other syntheses of this... 

The performance and excellent application profile of RCM are illustrated by the total synthesis of various resin glycosides and sugar-based macrodiolides such as tricolorins A and G, woodrosin I, and ipomoeassins B and E (Scheme 5.47). The synthesis of these amphiphilic natural products has resulted in the advancement of carbohydrate chemistry and is due to Ftirsner et al. who have recently reviewed their effort in this area [86]. In this review, they fully detail the syntheses of tricolorins A (208) (Equation 1, Scheme 5.47) and G (211) (Equation 2, Scheme 5.47), two natural products isolated from Ipomea tricolor, which are plant growth inhibitors... 

There are a few additional reports of truncation reaction products [11c, 20]. Rychnovsky et al. envisioned a possible double RCM within the coordination sphere of the Ca(II) biscarboxylate salt of the diene substrate 120 or of its relay-tethered analog 119 as an innovative approach to a synthesis of the dimeric C2-symmetric macrodiolide natural product SCH 351448 (121) (Scheme 9.28) [34]. Again, metal loading and relay within 119 were effective, but the internal cycb2ation was sufficiently slow that truncated 120 was the only product observed. Under slightly more forcing conditions, the parent diene 120 produced a monomeric macrocycbc lactone RCM product. 

---