| dc.description.abstract | A study was carried out to convert 1-tetralone
and some of its derivatives to the amines by
Leuckart reaction. In this reaction, the ketones
(1) 1-cetralone, (2) 5-methoxy-1 -tetra1 one,
(3) 6-methoxy-l-tetralone, (4) 7-methoxy-1-tetralone
and (5) 5,7-dimethyl-l-tetralone were converted to
the formyl derivatives. These formamides namely,
(la) 1,2,3,4-tetrahydro-l-naphthvl, (2a) 5-methoxy-
-1, 2,3,4-tetrahydro-1-naphthy1, (3a) 6-methoxy-
- 1,2,3,4-tetrahydro-1-naphthy1, (4a) 7-methoxy-1,2,3,
4-tetrahydro-l-naphthyl and (5a) 5,7-dimethy1-
- 1,2,3,4-tetrahvdro-l-n3phthyl formamides were then
hydrolyzed to their corresponding amines:- (lb)
1-aminotetralin , (2b) 1-amino-5-methoxytetra1in,
(3b) 1-amino-G-methoxytetralin, (4) l-.omino-7-
-methoxytetralin, and (5b) l-amino-5,7-dimethyltetral
This was carried out by both acidic (concentrated
hydrochloric acid) and basic (1C% aqueous NaOH)
conditions. The former gave yields ranging from 0%
to 75%, while the latter gave yields ranging from
90% to 97%. Acid hydrolysis of 3a and 4a gave
black-gummy compounds and no amines were obtained.
This showed that hydrolysis of formyl derivatives
under basic conditions gave better results and is
recommended.
(vi)
Suitability of these 1-tetralinyl groups as
potential carboxamide protecting -for asparagine
and glutamine side chain amide groups were investigated.
The amines lb,2b,3b,4b and 5b were used as
precursors to prepare the carboxamide protected
derivatives namely, (6) Boc-Gln(1,2,3, 4-tetrahydro-
-l-naphthyl)-a-OBzl, (7 ) Boc-Asn(1,2,3,4-tetrahydro-
«
-1-naphthyl)-B-OBzl, ( 8 ) Boc-Gln(5-methoxy-
-1,2,3,4-tetrahydro-l-napnthyl)-a-OBzl, (9 ) Boc-Asn-
(5-methoxy-1,2,3,4-tetrahydro-1-naphthyl)-B-OBzl,
tl Q) Boc-Gln(6-methoxy-l,2,3, 4-tetrahyd ro-l-napthy1)-
-a-OBzl, (11) Boc-Asn (6-methoxy-1,2,3, 4-tet rahydro-
-1-naphthyl)-a-0Bzl, ( 12) Boc-G1n(7-methoxy-1,2,3,4-
-tetrahydro-l-naphthyl)-a-OBzl, ( 13 ) Boc-Asn-
-(7-methoxy-l,2,3,4-tetrahydro-l-naphthyl)-a-0Bzl,
(14 ) Boc-Gln(5,7-dimethyl-l,2, 3,4-tetrahydro-l-
-naphthyl)-a-0Bzl,(15) Boc-Asn(5,7-dimethyl-l,2,3,4-
-tetrahydro-l-naphthyl)-g-OBzl. The N,N'-dicyc-
-lohexylcarbodiimide/N-hydroxysuccinimide (DCC-HONSU)
coupling methoO gave yields ranging from 40% to 86%.
These carboxamide protected derivatives were subjected
to cleavage studies in TFA-Ch^C^-anisole (50:46:2-
v/v) . The protecting groups in glutamine derivatives
(6, 6,10,12. and 14) were removed within 24hr. In
the carboxamide protected derivatives of asparagine
(7 , 9,11,13 andl5), the protecting groups in 9
and 11 were found too labile to be used during
(vii)
peptide synthesis. The protecting groups in 7 ,
13 and 15 were stable in the above deprotecting
reagent upto 24hr. These derivatives (7 , 13
and 15)were therefore subjected to cleavage studies
in boron trifluoride complex with acetic acid (BTFA).
This completely removed the protecting . groups. The
group in 7 was cleaved completely after 4hr, in
13 after 3hr and in 15 after 3hr. This showed that
the groups 1,2,3,4-tetrahydro-1-naphthyl,7-methoxy-
-1,2,3,4-tetrahydro-l-naphthy1 and 5,7-dimethyl-
-1,2,3,4-tetrahydro-l-naphthyl were found to be
potential carboxamide protecting groups due to their
stability in TFA-CH2Cl2-anisole (50:48:2 v/v) and
their easy cleavage by BTFA.
The carboxamide protected derivatives whose
protecting groups were found promising (7.,13 and
15Jwere used in the synthesis to the dipeptides
Boc-Phe-Asn(1,2,3,4-tetrahydro-1-naphthyl)-g-OBzl,
Boc-Phe-Asn(7-methoxy-1,2,3,4-tetrahydro-1-naphthyl)-
-a-OBzl and Boc-Phe-Asn(5,7-dimethy1-1,2,3,4-
-tetrahydro-l-naphthyl)-g-OBzl. The carboxamide
protecting groups in these dipeptides also behaved in
the same way as in 7,13 and 15. These dipeptides were
used in .synthesis to the tripeptides, Boc-Ile-Phe-Asn-
(1,2,3,4-tetrahydro-1-naphthyl)-6-OBzl, Boc-I1e-Phe-Asn-
(7-met hoxy-1, 2, 3, 4-tetrahydro-l-naphthyl) -ct^CBzl and
Boc-I1e-Phe-Asn(5,7-dimethyl-1,2,3,4-tetrahydro-1-naphthyl
)- B-OBzl . | |
