Malyngolide

The unique power of Hoveyda s recyclable ruthenium catalyst D in RCM with electron-deficient and sterically demanding substrates is illustrated in Honda s total synthesis of the simple marine lactone (-)-malyngolide (54), which contains a chiral quaternary carbon center (Scheme 10) [35]. Attempted RCM of diene 52 with 5 mol% of NHC catalyst C for 15 h produced the desired... 

Scheme 10 The power of Hoveyda s catalyst D in total synthesis of malyngolide (54) [35]...

Trost used a rhodium(i)-catalyzed hydroboration to obtain a key intermediate 139 in 90% yield in the synthesis of the pyrone ring of the natural product (—)-malyngolide 140 (Scheme 17).143... 

Scheme 4.48 Asymmetric synthesis of/i-allenic acids 184,186 and (-)-malyngolide 187 via /Mactones.

Scheme 19.34 (-)-Malyngolide. (a) 10mol% 180, EtCOBr, / Pr2NEt, CH2CI2, -50°C (b) C9Hn9MgBr, 10 mol% CuBr, THF, -78°C ...

Inda-box ent-9a has been used recently in the production of the natural product (-)-malyngolide 265. " The key step of the synthesis by Ghosh and Shirai, as shown in Figure 9.80, is the hetero-Diels-Alder reaction of Danishefsky s diene 112 and cx-ketoester 263 to afford the pyranone derivative 264 in 77% yield and 47% ee that was converted into (—)-malyngolide in several additional steps. The preparation of different pyranones was investigated using different ot-ketoesters. 

Analogous to the use of chiral enoates (see previous section), a, -unsaturated carboxylic amides, prepared from chiral amines, may be utilized in asymmetric 1,4-additions. When Grignard reagents are added to unsaturated amides (21), derived from (-)-ephedrine (20),25 highly optically active fi-sub-stituted alkanoic acids (22 R and R = alkyl or phenyl) are obtained in a variety of cases, after hydrolysis of the initially formed adducts (Scheme 7). This method was used for the synthesis of the antibiotic (-) malyngolide and its stereoisomers.26 Recrystallization of the intermediate (saturated) amide was necess-... 

This reductive coupling reaction is a useful route to 5-substituted 5-lactones such as malyngolide (1), an antibiotic obtained from blue-green algae.3... 

Magnesium methyl carbonate, 310 Malic acid, 135 Malyngolide, 224, 316 Manganese(II) chloride-lithium aluminum hydride, 310 Manganese dioxide, 311 Manicone, 121... 

Trost, B. M. Tang, W. Schulte, J. L. Asymmetric synthesis of quaternary centers. Total synthesis of (-J-malyngolide. Org. Lett. 2000, 2, 4013-4015. 

Cardellina, J. H., II, Moore, R. E., Arnold, E. V., and Clardy, J., Structure and absolute configuration of malyngolide, an antibiotic from the marine blue-green alga Lyngbya majuscula Gomont, J. Org. Chem., 44, 4039, 1979. 

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

The reaction of a chiral Grignard reagent derived from ephedrine with the oxathiane 2 was used to prepare the 8-hydroxy acid 5 in 34% overall yield. On standing, 5 lactonizes to (— )-malyngolide (6). ... 

The method has been applied to the diastereoselective synthesis of naturally occurring compounds such as frontalin (84-100% ee) and(—)-malyngolide (95% ee). On the other hand, diastereoselective alkylation of chiral formylaminal with Grignard reagents and the subsequent hydrolysis afford optically active S-a-hydroxyaldehydes with moderate stereoselectivity (60% ee). ... 

The reaction of isoprene monoxide with a range of alcohol pronucleophiles in the presence of the ligand (3 mol%), Pd2dba3.CHCl3 (1 mol%) and triethylboron (1 mol%) gave the glycol monoethers in excellent yield and enantiomeric excess. The use of p-methoxybenzyl alcohol and 3-nonyl-3,4-epoxybut-1-ene afforded an intermediate that was converted into (—)-malyngolide (eq 8). ... 

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