Chain synthesis strategy

Saito examined the dihydroxylation of a collection of bis-allylic ethers, including 294 (Equation 49) and 296 (Equation 50) [202], in the context of a two-directional chain synthesis strategy [203]. Exceptionally high levels... 

Figure 1. Synthesis of a chemical repeating unit of the Shigella flexneri variant Y O-antigen, employing a sequential chain extension strategy.

Apart from dehydration of glucose or fructose in the presence of alcohols and acid catalysts, synthesis strategies via 5-(chloromethyl)furfural and subsequent heating in the desired alcohol or utilizing furfuryl alcohol as feedstock have been demonstrated [89-98], While 5-(chloromethyl)furfural may be derived in one step based on cellulose, a synthesis procedure starting from furfuryl alcohol utilizes hemicellulose as feedstock, bridging the C5 and C6 carbohydrate value chain. 

Recently, the discovery of polymerase chain reactions (PCR) by K. B. Mullis [4] in 1985 clearly demonstrates that in vitro , abiotic construction of DNA in a flask by these genealogical directed synthesis strategies is presently a routine and significant commercial process. These genealogically directed syntheses lead to an extramolecular proliferation of molecular level progeny. 

The precursor tetratosylamide 22 may be prepared in five steps from ethylenediamine. The reaction sequence (Scheme 3.7) involves diacylation of ethylenediamine with 3-thiadiglycollic anhydride, followed by esterification, ammonolysis, borane reduction and toluenesulfonylation.12 This stepwise synthesis of the desired tetratoluenesulfonamide involving a simple chain elongation strategy is reminiscent of the syntheses of large ring aza-oxa crowns (e.g. [24]-N404) discussed in Chapter 2. 

With the advent of efficient cross metathesis catalysis, this reaction is being seen in a variety of total syntheses and analogue synthesis strategies. Two areas where cross metathesis has been particularly useful are the addition of side chains or heterodimerization and the formation of homodimers. 

Fig. 3 (29—32). A minor disadvantage of this method is that it produces protected cyclized peptide, which must be purified, deprotected, and then purified again. The backbone amide and side-chain attachment strategies alleviate this, as synthesis on resin is followed by a combined deprotection/cleavage step. However, these strategies produce the cyclic peptide in solution as a complex mixture with scavengers and cleaved protecting groups (Fig, 4). As a consequence, all these methods require a significant effort to be spent on purifying the cyclic peptide after synthesis.

SCHEME 13.51 Schreiber s synthesis of (—)-hikizimycin featuring a two-directional chain-elongation strategy involving an aldehyde olefination and face-selective dihydroxylations. 

Ikemoto, N, Schreiber, S L, Total synthesis of (—)-hikizimycin employing the strategy of two-directional chain synthesis, J. Am. Chem. Soc., 114, 2524-2536, 1992. 

As a rule, peptidases can only make a meaningful contribution to a synthesis strategy if the full advantagee of the enzymatic reactions can be utilized. An a priori completely unrealistic position is the comparison of a stepwise peptidase-catalyzed assembley of a peptide chain with the automatic solid-phase technique. 

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