Tbutyl Esters of Amino Acids and Peptides and Their Use in Peptide Synthesis
J uly 5 , 1960
& BUTYL STERS PEPTIDEYNTHESIS
E
IN
S
g roup occupies t he same position of the peptide chain in both mercaptalbumin and non-mercaptalbumin.
3359
Acknowledgments.-The authors are grateful to
Mrs. J . O’Brien and Mr. 0. Griffith for their technical assistance.
[ CONTRIBUTION T HE O RCAXIC
FROM
CHEMICAL
RESEARCH
SECTION,
LEDERLE
LABORATORIES v r s r o x , MERICAN VASAMID
U~
A
C
R
Co., PBARLIVER,X. Y . ]
&Butyl Esters of Amino Acids and Peptides and their Use in Peptide Synthesis1
BY GEORGEv. ANDERSON i A ND
FRANCIS. C.4LLAHAN
M
R ECEIVED
NOVEMBER 1959
30,
T he s ynthesis of t-but)-1 esters of amino acids and peptides and their use in peptide synthesis is described. T h e most convenient method was the acid-catalyzed reaction of isobutylene with benzyloxycarbonylamino acids or peptides followed by catalytic hydrogenation to produce the basic esters. Another general method entailed the u se of silver salts and t-butyl iodide. &Butyl esters are particularly useful in peptide synthesis in t h a t the ester group may be removed by acid catalysis and thus side reactions encountered in alkaline hydrolysis may be avoided. Other advantages arise from the stability of a mino acid or peptide esters a s free bases, particularly in allowing their storage and use as such. Comparative stabilities to ethyl esters are reported in s everal examples. T h e synthesis of several t-butyl peptides is reported a s well a s selective removal of this ester group or of amine-protecting groups when both are present.
I n recent years naturally occurring peptides with high biological activities in such diverse fields as antibiotics, bacterial growth factors, hormones, smooth muscle stimulants and pain-producing subs tances have been isolated. Synthesis of such peptides has not kept up with structure determination largely because present methods are time-consuming and frequently give poor yields.2 As p art of an
& BUTYL STERS PEPTIDEYNTHESIS
E
IN
S
g roup occupies t he same position of the peptide chain in both mercaptalbumin and non-mercaptalbumin.
3359
Acknowledgments.-The authors are grateful to
Mrs. J . O’Brien and Mr. 0. Griffith for their technical assistance.
[ CONTRIBUTION T HE O RCAXIC
FROM
CHEMICAL
RESEARCH
SECTION,
LEDERLE
LABORATORIES v r s r o x , MERICAN VASAMID
U~
A
C
R
Co., PBARLIVER,X. Y . ]
&Butyl Esters of Amino Acids and Peptides and their Use in Peptide Synthesis1
BY GEORGEv. ANDERSON i A ND
FRANCIS. C.4LLAHAN
M
R ECEIVED
NOVEMBER 1959
30,
T he s ynthesis of t-but)-1 esters of amino acids and peptides and their use in peptide synthesis is described. T h e most convenient method was the acid-catalyzed reaction of isobutylene with benzyloxycarbonylamino acids or peptides followed by catalytic hydrogenation to produce the basic esters. Another general method entailed the u se of silver salts and t-butyl iodide. &Butyl esters are particularly useful in peptide synthesis in t h a t the ester group may be removed by acid catalysis and thus side reactions encountered in alkaline hydrolysis may be avoided. Other advantages arise from the stability of a mino acid or peptide esters a s free bases, particularly in allowing their storage and use as such. Comparative stabilities to ethyl esters are reported in s everal examples. T h e synthesis of several t-butyl peptides is reported a s well a s selective removal of this ester group or of amine-protecting groups when both are present.
I n recent years naturally occurring peptides with high biological activities in such diverse fields as antibiotics, bacterial growth factors, hormones, smooth muscle stimulants and pain-producing subs tances have been isolated. Synthesis of such peptides has not kept up with structure determination largely because present methods are time-consuming and frequently give poor yields.2 As p art of an