Aldehydes blocking

Several blocked diamines or amino-alcohols are commercially available. The aldimine is an aldehyde-blocked diamine. The ketimine is a ketone-blocked diamine. The oxazolidine is a five-membered ring containing oxygen and nitrogen. The oxazolidine ring shown below is an aldehyde-blocked amino alcohol. The basic synthetic concepts of an aldimine, a ketimine, and an oxazolidine are shown below ... 

A more general method for carbohydrates that can be used equally well on handsections and on sections of plastic embedded materials uses the Periodic acid SchifFs (PAS) reaction or one of its variants [29] for vicinal hydroxyl groups [22,23]. Sections are treated with 1%W/V Periodic acid at room temperature for 10 minutes and rinsed. The aldehydes created by this treatment are detected with SchifFs reagent (decolorized para-rosaniline) by immersion for 30 minutes. A red color (or fluorescence with excitation at 540 nm) indicates vicinal hydroxyl groups in starch and many other carbohydrates. If the specimen has been fixed with aldehydes then an aldehyde-blocking step must precede this reaction [22]. The best treatment is immersion for 24 hr in a saturated solution of dimedone. 

Hydrolysis of the trialkyl silyl groups gives poly(vinyl alcohol). Block copolymers in which one block is poly( vinyl alcohol) can be synthesized if a telechehc with an aldehyde terminal group is used to initiate the aldol GTP structures such as polyfsty-rene-h/oc -vinyl alcohol) can be prepared in this way. Alternatively, as silyl ketene acetals can react with aldehydes, block structures can be formed by a coupling process. 

This technique, modified from our original method (Reid et al. 1973), utilizes Lillie and Pizzolato s (1972) borohydride aldehyde blocking method. 

Generating Haworth formulas to show stereochemistry m furanose forms of higher aldoses is slightly more complicated and requires an additional operation Furanose forms of D ribose are frequently encountered building blocks m biologically important organic molecules They result from hemiacetal formation between the aldehyde group and the C 4 hydroxyl... 

With aldehydes, primary alcohols readily form acetals, RCH(OR )2. Acetone also forms acetals (often called ketals), (CH2)2C(OR)2, in an exothermic reaction, but the equiUbrium concentration is small at ambient temperature. However, the methyl acetal of acetone, 2,2-dimethoxypropane [77-76-9] was once made commercially by reaction with methanol at low temperature for use as a gasoline additive (5). Isopropenyl methyl ether [116-11-OJ, useful as a hydroxyl blocking agent in urethane and epoxy polymer chemistry (6), is obtained in good yield by thermal pyrolysis of 2,2-dimethoxypropane. With other primary, secondary, and tertiary alcohols, the equiUbrium is progressively less favorable to the formation of ketals, in that order. However, acetals of acetone with other primary and secondary alcohols, and of other ketones, can be made from 2,2-dimethoxypropane by transacetalation procedures (7,8). Because they hydroly2e extensively, ketals of primary and especially secondary alcohols are effective water scavengers. 

Macrolides containing only neutral sugars were obtained from a platenomycin-producing organism (217,218). Four demycarosyl derivatives of platenomycins were isolated from biosyntheticaHy blocked mutants of S. platensis, two of these possessed a methyl group rather than an aldehyde (219). A pair of novel compounds related to carbomycin were isolated in which one contained an unusual 10,ll-dihydro-12,13-diol moiety, the other a 14-hydroxy-epoxyenone moiety (220). 

This catalyst was successfully applied to the Diels-Alder reaction of propargyl aldehydes as dienophUes [12] (Scheme 1.21, Table 1.8). Though 2-hutyn-l-al and 2-oc-tyn-l-al are unreactive dienophUes, silyl- and stannyl-suhstituted a,/ -acetylenic aldehydes react with cydopentadiene readily in the presence of 20 mol% of the catalyst at low temperature to give hicyclo[2.2.1]heptadiene derivatives in high optical purity these derivatives are synthetically useful chiral building blocks. 

Synthesis gas is also an important building block for aldehydes from olefins. The catalytic hydroformylation reaction (Oxo reaction) is used with many olefins to produce aldehydes and alcohols of commercial importance. 

Penicilloic acid 5, the substrate for the projected lactamization reaction, could be derived from the suitably protected intermediate 6. Retrosynthetic disassembly of 6, in the manner illustrated, provides D-penicillamine hydrochloride (7) and tert-butyl phthalimido-malonaldehydate (8) as potential building blocks. In the synthetic direction, it is conceivable that the thiol and amino groupings in 7 could be induced to converge upon the electrophilic aldehyde carbonyl in 8 to give thiazolidine 6 after loss of a molecule of water. 

The adjacent iodine and lactone groupings in 16 constitute the structural prerequisite, or retron, for the iodolactonization transform.15 It was anticipated that the action of iodine on unsaturated carboxylic acid 17 would induce iodolactonization16 to give iodo-lactone 16. The cis C20-C21 double bond in 17 provides a convenient opportunity for molecular simplification. In the synthetic direction, a Wittig reaction17 between the nonstabilized phosphorous ylide derived from 19 and aldehyde 18 could result in the formation of cis alkene 17. Enantiomerically pure (/ )-citronellic acid (20) and (+)-/ -hydroxyisobutyric acid (11) are readily available sources of chirality that could be converted in a straightforward manner into optically active building blocks 18 and 19, respectively. 

With the key building blocks 16-19 secured, attention can now be turned to their coupling and elaboration to the cyclic heptaenone 6 (Scheme 4), from which both amphoteronolide B (2) and amphotericin B (1) could be generated. To this end, the advanced intermediates, hydroxy aldehyde 13 and ketophosphonate carboxylic acid 14 (Scheme 4), were synthesized as outlined below. 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

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