Glyco-amino acid synthesis

Several combinatorial approaches for the synthesis of glyco-amino acids have been developed, due to the complexity of carbohydrate conjugates. The synthetic challenge is to get access to these building blocks by automated synthesis in order to generate glycopeptides library, to fully understand their biological roles and to widen their use in medicinal chemistry. 

SCHEME 10. Synthesis of H2N-(Thr)2-(LacNAc-a-Thr)-(Thr)2-Gly-OH. Conditions (i) H2, Pd(C), MeOH-AcOH (10 1), 1 h (ii) 20% piperidine in DMF (iii) Fmoc-Thr, (benzotriazol-l-yloxy)tripyrrolidi-nophosphonium hexafluorophosphate (PyBOP), IV-hydroxybenzotriazole (HOBt), ethyldiisopropylamine (DIPEA) (iv) Glyco-amino acid 64, PyBOP, HOBt, DIPEA (v) TFA (vi) NaOMe, MeOH. 

Remarkable advances have been made in the synthesis of N- and O-glycosylated amino acids that, in addition to the 5-fattyacyl-cysteine, are the most sensitive derivatives to the conditions of peptide synthesis. The fine tuning of both carbohydrate and peptide chemistry as well as the use of enzymatic methods are required for the synthesis of glycopeptides. " Similarly soft chemistry has to be applied in the case of S-acylated peptides, whereas fat-tyacylation at amino groups raises no additional difficulties.The state of the art in the field of glyco- and lipopeptide synthesis is discussed in details in Vol. E22b, Sections 6.3 and 6.4, respectively. 

Tsutsumiuchi K, Aoi K, Okada M (1997) Synthesis of polyoxazoline-(glyco)peptide block copolymers by ring-opening polymerization of (sugar-substituted) alpha-amino acid N-carboxyanhydrides with polyoxazoline macroinitiators. Macromolecules 30(14) 4013-4017... 

N -Protection as allyl carbamate is used generally only for specific synthetic purposes where acid- or base-mediated deprotection procedures must be avoided or reduced to a minimal extent as in the case in the synthesis of glyco- and phosphopeptides (see Sections 6.3 and 6.5). Otherwise the orthogonality of this type of amino protection has been mainly exploited in side-chain protection to allow for selective chemistry such as selective acylations, e.g. cyclizations, to be performed on protected peptides in solution or in the resin-bound state (see Section 4.3.2.3.4). An additional interesting application of the Aloe group is the one-pot deprotection and acylation with carboxy components resistant to the paUadium(0)-catalyzed allyl cleavage by hydrostannolysis as reported in Section 4.3.2.3.4.P 1... 

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