Acetonide removal

Similarly, in another example, alkylation of 111 with diepoxide (—)-115 (1 equiv.) in the presence of HMPA (1.3 equiv.) furnished diol (+)-117. Protection of (+)-117 to form the acetonide, removal of the silyl protecting groups (TBAF), and hydrolysis of the dithiane with Hg(Cl04)2 provided the diketone (+)-118. Hydroxy-directed syn-reduction of both carbonyl groups with NaBI U in the presence of Et2BOMe, and triacetonide formation, followed by hydrogenolysis and monosilylation, afforded the desired Schreiber subtarget (+)-119, which was employed in the synthesis of (+)-mycoticins A and B (Scheme 8.31) [56b]. 

Scheme 17 shows the synthesis of a C-glucoglycerolipid. The secondary hydroxyl was capped (NaH, PMBBr) and the acetonide removed to deliver 51 (23). Diacylation then provided 52 which was deprotected to afford the target 53. Selective acylation of the primary hydroxyl was readily accomplished by simply using one equivalent of the acid chloride. 

For solid-phase synthesis of 26.4 (Figure 15.26), compound 26.1 was immobilized on the resin as for the previous example (loading 86%, 26.2). The free hydroxyl derivative obtained after the acetonide removal was subjected to crucial hetero-Michael reaction. The use of NaH as a base at room temperature provided the expected product 26.3. After cleavage from the support, the crude sample was purified giving product 26.4 (25% overall yield in four steps), which was further assigned by NMR. It was interesting to note that this unusual regio- and stereoselective hetero-Michael reaction worked in a similar manner as in solution synthesis. For comparison purposes, compound 26.5 was also synthesized in solution in a similar manner. 

For the final part (Scheme 5.3), the 20-carbon chain of fumonisin Bj was coupled from the Uthium acetylide derived from 273 and the Weinreb amide 279 (233). After enantioselective reduction of the alkynyl ketone 281 (234, 235), the C-10 stereochemistiy was set, followed by benzyl ether formation and acid-catalyzed acetonide removal, to provide diol 282 (236). Using tricarballylic acid dibenzyl ester, the two hydroxy groups were esterified (237) and the hydrogenation of the azide, the alkyne, and the benzylic ethers led to the target product, fumonisin Bj (249). The spectroscopic analysis matched with those of commercial fumonisin Bj and further experiments on the synthetic material showed inhibitoiy activity on sphingoUpid biosynthesis. 

PG structure Can remove PG but keep acetonide to produce A Conditions Can PG withstand HsO for acetonide removal to produce B ... 

The most ambitious application of this chemistry is in the ring closure to form 6-deoxyerythronolide B 3.104 (Scheme 3.45). Macrolides are most commonly prepared by lactonization of a hydroxy acid, so there is a need to carry the hydroxy functional group through the synthesis. The allylic CH activation method avoids this need, requiring just an alkene. Controlled by the conformation of the substrate, allylic oxidation of the precursor 3.101 provided a single diastereoisomer of the macrolide 3.103. A bis-sulfoxide 3.102 was found to be the optimum ligand for palladium. The macrolide 3.103 could be converted to 6-deoxyerythronolide B 3.104 by simultaneous reduction of the alkene and the PMP acetal, selective oxidation of one hydroxyl group, and acetonide removal. 

Clark etal. have compared the abihty of [Ru]-I and [Mo]-I catalysts to generate oxocines (Scheme 3.1) and oxepines (Scheme 3.2) from the neutral diene RCM reactions [13]. The precursors for these studies were prepared from the addition of the appropriate carbon nucleophile to D-glyceraldehyde, followed by acetonide removal and reprotection of the resulting triol as the cyclic acetal, to give 36. Ether and diene formation gave the metathesis precursor 37. A comparison of [Mo]-I and [Ru]-I catalysts revealed a similar efficiency for the synthesis of oxocine 38. 

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol, the 1,3-acetal is the preferred product, in contrast to the acetonide, which gives the 1,2-derivative. The benzylidene acetal has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared. ... 

To a suspension of 500 mg of 6a-fluoro-triamcinolone in 75 ml of acetone is added 0.05 milliliters of 72% perchloric acid and the mixture agitated at room temperature for 3 hours. During this period the crystals gradually dissolve and the clear solution is neutralized with dilute bicarbonate and the acetone removed in vacuo. The resulting crystalline suspension is filtered and the crystals washed with water. The dried material is recrystallized from 95% alcohol to give the pure acetonide. 

A solution of 50 mg of 6a-fluoro-triamcinolone acetonide in 1 ml of pyridine and 1 ml of acetic anhydride is allowed to stand at room temperature for 18 hours. Removal of the reagents in vacuo gives a crystalline residue which after crystallization from acetone-hexane gives the pure 16a,17a-isopropylidene 6o -fluoro-triamcinolone 21 acetate (fluocinonide), as described in U.S. Patent 3,197,469. 

At this point, completion of the total synthesis required removal of the three acetonides and the two silyl protecting groups (Scheme 18). Removal of the silyl groups with TBAF and subsequent treatment to acidic deprotection conditions led to complete deprotection of 110, but failed to provide filipin III. It was sus-... 

In order to ameliorate the problem of solvolytic degradation, compound 109 was treated with TIPSOTf, to provide silyl ether 113 in 72% yield (Scheme 19). The acetonides were removed with PPTS in warm MeOH to provide a mixture of compounds in which the TBS groups were also partially removed. Exposure of this mixture to HF-pyridine successfully generated filipin III (114), in 39 % overall yield from 113. 

To avoid the retro-Diels-Alder reaction, 56 was dihydroxylated prior to the introduction of the bromine atom (57). Removal of the acetonide group followed by cleavage of the diol afforded a bis-hemiacetal. Selective reduction of the less-hindered hemiacetal group gave 58. The remaining hemiacetal was protected, and the ketone was converted to an enol triflate, thus concluding the synthesis of the electrophilic coupling component 51. 

PREPARATION OF (OH)4- [G2]-C02CH2C6H5 [13]AND GENERAL PROCEDURE FOR THE REMOVAL OF THE ACETONIDE PROTECTING GROUPS... 

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