Synthesis of the glycotripeptide alanyl‐(O‐β‐D‐galactopyranosylseryl)‐alanine using (9‐fluorenylmethoxy)carbonyl and esters of 2‐(hydroxymethyl)‐9,10‐anthraquinone as temporary protecting groups

The cesium salts of N‐[(9‐fluorenylmethoxy)carbonyl]‐L‐serine (Fmoc‐Ser, 1a)*** and ‐L‐threonine (Fmoc‐Thr, 1b) were treated with 2‐(bromomethyl)‐9,10‐anthraquinone (Maq‐Br), yielding Fmoc‐Ser‐OMaq (2a, 79%) and Fmoc‐Thr‐OMaq (2b, 74%). HgBr2‐catalyzed glycosylation with 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐galactopyranosyl bromide gave Fmoc‐Ser(Ac4βGal)‐OMaq (3a, 89%) and Fmoc‐Thr(Ac4βGal)‐OMaq 13b, 53%). Fmoc‐Ser(Ac4βGal)‐OH (4), obtained by reaction of 1a with Na2S2O4 (88%), was condensed with H‐Ala‐OMaq using the DCC/HOBt method (83%). The Fmoc‐Ser(Ac4βGal)‐Ala‐OMaq(5), thus obtained, was Nα‐deprotected with morpholine and coupled with Fmoc‐Ala using water soluble carbodiimide in the presence of HOBt to yield Fmoc‐Ala‐Ser(Ac4βGal)‐Ala‐OMaq (6, 59%). The fully deprotected glycotripeptide (8) was obtained from 6 by successive treatment with Na2S2O4, morpholine and hydrazine hydrate (81%). The compounds 3a, 6 and 8 were characterized using correlated 300 MHz 1H NMR spectroscopy (2D‐COSY).