Malic acid triol

Fig. 9.18. Regioselective acetalizations of a 1,2,4-triol ("malic acid triol").

An important polyalcohol for regioselective acetalizations is the triol of Figure 9.18 because it can be easily obtained from S-malic acid. This substrate contains both a 1,2-diol and a 1,3-diol. Each of these subunits can be incorporated into an acetal selectively—depending on the carbonyl compound with which the acetalization is carried out ... 

The macrocyclic framework was constructed beginning with 4, available from (-i-)-citronellol, and 5 obtained from (-)-)-malic acid. Kolbe reductive coupling and reacylation then gave the coupled ester 6 in 42% yield. Reduction of this material to the triol followed by protection of the 1,2 diol as the acetonide and Collins oxidation gave the desired aldehyde 7. 

The phosphonium salt 175 requires similar operations but malic acid 34 is reduced to the triol 180 before selective protection 181 leaves just one alcohol for conversion to tosylate, bromide and finally protected phosphonium salt 182. 

Hydroxyproline is abundant but hydroxylysine is not. Fortunately it can be made59 from an abundant member of the chiral pool - malic acid 34. Borane reduction gives the triol 332 and anisaldehyde gives the diequatorial acetal 333 under thermodynamic control. 

By far the most widely used chiral intermediates derived from malic acid are acetals of 1,2,4-butanetriol. Triol 370 is by its nature capable of forming acetals with either the C-1 and C-2 hydroxyls, thus producing a 5-membered ring, or with the C-2 and C-4 hydroxyls to give a... 

The central ring (777) of elaiophylin, a macrodiolide antibiotic isolated from fungi, is synthesized from (iS)-malic acid via triol 767 as shown in Scheme 111 [167]. Since the ring is C2-symmetric, only half the molecule need be prepared. 

R)-Malic acid can be selectively protected as a dioxolanone (904). Treatment of 904 with excess methyl magnesium iodide affords lactone 905 as the result of a completely regiose-lective reaction of Grignard reagent with the dioxolanone carbonyl followed by lactonization (Scheme 133) [201]. Reduction of the lactone with lithium aluminum hydride gives triol 906, which is converted to iodoacetonide 907 (OH OTs I). This intermediate is used to supply the chiral side chain for the steroid 24,25-dihydroxycholecalciferol. 

---