Fmoc-Ser

Synthesis of the corresponding purine nucleoamino acids Fmoc-Ser " - and Fmoc-Ser " - via the O-MTM ether 3 was compromised by a lack of re-gioselectivity during the l2-raediated nucleosidation. The incorporation of these nucleoamino acids into aPNAs is also problematic because of facile acid-catalyzed depurination. The latter problem could be traced to the -CH2-O-CH2- linker [38]. We decided to circumvent the problem by synthesizing the isosteric norvalinyl... 

To summarize, practical syntheses of the protected pyrimidine nudeoamino acids Fmoc-Ser -OFl (6) and Fmoc-Ser " ° -OH (9) as well as the purine nucleoamino acids Fmoc-Nva -OFl (15) and Fmoc-Nva -OH (18) have been developed. We are poised to prepare aPNAs containing all four DNA nudeobases. 

Fmoc-Ser(fiu)-OH, PfPyU, DIEA, sym-collidine, HOAt, NMP Ac20, pyridine. 

H Mostafavi, S Austermann, W-G Forssmann, K Adermann. Synthesis of phospho-urodilatin by combination of global phosphorylation with the segment coupling approach. (Fmoc-Ser-OH + TBTU + H-Xaa-OR) Int J Pept Prot Res 48, 200, 1996. 

A Di Fenza, M Tacredi, C Galoppini, P Rovero. Racemization studies of Fmoc-Ser(tBu)-OH during stepwise continuous-flow solid-phase peptide synthesis. Tetrahedron Lett 39, 8529, 1998. 

An alternative procedure has been proposed for the direct synthesis of Fmoc-SeC-(Mob)-OH that is based on activation of Fmoc-Ser-OAL as the O-tosylate followed by reaction with 4-methoxybenzyldiselenide reduced in situ with hypophosphoric add to the selenol. 59 Selective reductive cleavage of the allyl ester generates Fmoc-SeC(Mob)-OH in good yields. 

Fmoc-Ser/Thr-OtBu esters and cleave the ester to provide a building block suitable for synthesis 43,163] The use of Fmoc amino adds, where the a-carboxy group of the amino acid is unprotected, has also been reported,[164 1671 as well as use of the corresponding O Donnell Schiff bases 516]... 

Fmoc-Ser-OPfp or Fmoc-Thr-OPfp AgOTf, CH2CI2, 3-A molecular sieves —40 to -30 °C, 8 h... 

Fmoc-Ser-OBzl or Fmoc-Thr-OBzl MeOTf, CH2CI2, 4-A molecular sieves rt, overnight... 

A"-Fmoc-Ser 0-[3,4,6-tri-0-benzyl-2-0-(2,3,4,6-tetra-0-benzyl-a-D-mannopyranosyl)-a-maimopyr-anosyl])-OBzl (15, R1 = H) 250 ... 

JV -Fmoc-Ser-(3,4,6-tri-0-acetyl-2-deoxy-2-iodo-a-D-mannopyranosyl)-OBzl (27) 13 ... 

Fmoc-Ser-OPfp or Fmoc-Thr-OPfp AgOTf, CH2CI2... 

The synthesis of the linear octapeptide was performed applying Fmoc/tBu chemistry and starting from 0.82 g (0.39 mmol-g-1, 0.32 mmol) of Fmoc-Ser(tBu)-HMPAA-resin (Millipore). Iturinic acid was coupled as the jV-Boc derivative. After deprotection and cleavage with TFA/H20 (95 5), the product was purified by preparative RP-HPLC yield 37 mg (74%). 

Figure 1 Proportion of the Xaa(P)-Deleted Peptide, ASQGLEDPA-NH2, Determined in Crude Products Obtained from the PyBroP/DIPEA, BOP/HOBt/NMM, BOP/HOBt/DIPEA, HBTU/HOBt/DIPEA, HATU/ HOAt/DIPEA, and HATU/DIPEA Coupling of Fmoc-iyr[PO(OBzl)(OH)]-OH (Y), Fmoc-Ser[PO-(OBzl)-(OH)]-OH (S), and Fmoc-Thr[PO(OBzl)(OH)]-OH (T) (3 equiv) for 1 hJ4Sl b...

Fmoc—Ser—OPac ------------------------------------ - Fmoc—Ser[PO(OBzl)(OTce)]—OPac... 

The incorporation of derivatives Fmoc-Ser[PO(OBzl)(OH)]-OH (18) and Fmoc-Thr[PO(OBzl)(OH)]-OH is best effected using uronium reagents such as HBTU/HOBt/ DIPEA and HATU/HOAt/DIPEA since both BOP and PyBroP failed to effect complete incorporation in comparative test couplings. 48 In a separate work, the BOP/HOBt/DIPEA coupling of Fmoc-Ser[PO(OBzl)(OH)]-OH was found to be only 85% complete after double coupling and the incorporation of the anionic phosphorodiester caused a decrease in the coupling efficiency of following residues. 94 Despite these potential problems, both Fmoc-Ser[PO(OBzl)(ONa)]-OH and Fmoc-Thr[PO(OBzl)(ONa)]-OH have been successfully employed for the Fmoc-based solid-phase synthesis of various Ser(P)- and Thr(P)-... 

Table 6 Ser(P)- and Thr(P)-Peptides Prepared Using Fmoc-Ser[PO(OBzl)(OH)]-OH and Fmoc-Thr[PO(OBzl)(OH)]-OH[26-48-84 )2 )3l...

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