9-Fluorenylmethyloxycarbonyl derivatives

In the case of vancomycin [72], an original study was performed to obtain a well-defined stationary phase structure, since it was reasonably assumed that the antibiotic is randomly linked to the silica by one or both of its amino groups, one belonging to the disaccharide portion (primary), and the other one to the heptapeptide core (secondary). Thus, alternate fluorenylmethyloxycarbonyl (FMOC)-amino-protected derivatives were prepared and immobilized in a packed column, and then vancomycin was recovered by cleavage of the protecting groups. The two defined CSPs obtained, when compared with the CSP produced from native randomly linked vancomycin, showed lower retention and enantioselectivity, also if they still separated the same compounds. Thus, no advantages could be found to choose these phases as an alternative to the native vancomycin CSP. 

Other related reactions involve TV-fluorenylmethyloxycarbonyl (N-Fmoc) AAs and aliphatic aldehydes (83JOC77) or substituted /-butoxycarbonyl (N-Boc) Aas and 2,2-dimethyoxypropane (acetone dimethyl ketal) (84TL5855 87JOC2361 88TL2019), as well as A-(dimethylthio)methylene derivatives of an AA and aromatic aldehydes [89JCS(P1)1577]. 

Treatment of cycloserine with Fmoc-Cl or Fmoc-OSu in the presence of pyridine afforded a mixture of endo- and exocyclic N-acylated products (Fmoc = 9-fluorenylmethyloxycarbonyl). Selective protection of the primary amine was achieved on multigram scale and in high yield by in situ formation of the bis-silylated derivative with T,0-bis(trimethylsilyl)acetamide (BSA) followed by acylation (Scheme 76) <1998T15879>. 

The C-4 acids (183 and 184) have also been subjected to borane reduction conditions to afford alcohol 195 in 23-50% yield or 64% yield as the C-8 epimeric mixture (195 and 196, Scheme 29) [34, 49, 64]. The C-8 alcohol epimers 195 and 196 have been treated separately as a common intermediate for a number of C-4 derivatives including esters, ethers, and amines [34, 49, 64], Alcohols 195 and 196 was subjected to DCC, DMAP, and desired acid chloride or carboxylic acid in CH2CI2 affording ester analogs in 50-92% yield [64], Esters prepared include alkyl, aryl, and fluorenylmethyloxycarbonyl (Fmoc) protected amino acid derivatives (197 and 198) [64]. Ethers were prepared with various alkyl halides and Ag20 in CH3CN at 40 °C. Alkyl, allyl, and benzyl ethers were prepared in 45-80% yield (199 and 200) [34,64]. Alcohols 195 and 196 were then activated to the triflates and displaced by a variety of amines by treatment with trifluoromethanesulfonic anhydride and desired amine in 22% - quantitative yield over two steps (201 and 202)... 

A class of zinc ion (Zn2+) sensors, which utilized an unnatural amino acid that included the chelation-sensitive fluorophore, 8-hydroxy-4-(Af,Af-dimethylsulfonamido)-2-methylquinoline (sulfonamido oxine (Sox), Figure 1.3a), provided inspiration for a second class of kinase activity sensors [12-14]. The Sox amino acid was prepared via asymmetric synthesis and converted to the fluorenylmethyloxycarbonyl (Fmoc)-protected derivative and incorporated via SPPS into a peptide containing a proline-mediated fi-turn sequence [13]. The fl-turn was flanked by both Zn-chelating amino acids and the Sox fluorophore (Figure 1.3b). In this case, the fi-turn was included to provide preorganization... 

In yet another example (Scheme 12.79), if the 9-fluorenylmethyloxycarbonyl (fMOC) derivative of glycine (Gly, G) were allowed to react with the ethyl ester of valine (Val, V) in the presence of 5-nitro-3H-2,3-benzoxathiole S,S-dioxide, the peptide would again form and the nitrophenol generated from the coupling reagent is easily removed as a consequence of its acidic properties. 

Amino groups are often protected as their terf-butyloxycarbonyl amide (Boc) or fluorenylmethyloxycarbonyl amide (Fmoc) derivatives. The Boc protecting group is introduced by reaction of the amino acid with di-fi rt-butyl dicarbonate in a nucleophilic acyl substitution reaction and is removed by brief treatment with a strong acid such as trifluoroacetic acid, CF3CO2H. The Fmoc protecting group is introduced by reaction with an acid chloride and is removed by treatment with base. 

Fmoc derivative (Section 26.7) A fluorenylmethyloxycarbonyl N-protected amino acid. 

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