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Optical Induction During Biomimetic Formation of Cysteine.

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residue purified by chromatography on silica gel
(eluant : chloroform/methanol 9 : I). The NMR spectrum of
the oil obtained in this way (in CDC13) contains signals for
both ( 2 a ) and ( 2 b ) [ ( 2 ~ ) : ( 2 6 ) = 8 . 5 : 1 . 5On
] . rubbing with
ethyl acetatejether, 290mg of ( 2 a ) crystallized; m. p. 105-110°C (from ethyl acetate/ether); [a];'= -55'- (c=0.985 in
CHC13), yield 77%.
Optical Induction During Biomimetic Formation of
Cysteine[**l['I
By Ulrich Schmidt and Elisaheth Ohler[*]
The peptide hormones kallidin, eledoisin, and p-melanotropin contain ~-serine-~-proline
segments, and L-cysteinyl-Lproline units are found in the hormones p-corticotropin releasing factor, oxytocin, isotocin, vasopressin, and vasotocin. pMethyl-D-cysteinyl-L-proline is a component of a heterodetic
cyclotetrapeptide in the antibiotics nisin and subtilin13'. The
thioether of this ring is probably formed by intramolecular
addition of a mercapto group to the double bond of aminocrotonic acid in a-aniinocrotyl-L-prolylglycyl-~-cysteine.
This suggests that the spatial course of addition of hydrogen
sulfide or thiols to dehydroalanine-an essential reaction for
cysteine biosynthesis-can be directed by an amino acid joined
by a peptide-type linkage to dehydroalanine. This concept
is confirmed by a simple model : N-benzyloxycarbonyldehydroalanyl-r-prolinemethylamide ( I ) adds methanethiol in a
sodium methanethiolate-catalyzed reaction to give almost
exclusively (optical yield at least 85 %) N-benzyloxycarbonylS-methyl-~-cysteinyl-~-prolinemethylamide
(2a). The starting compound (1) was prepared according to the method
of P a t c h ~ r n i k ' ~
by] reaction of ( 2 h ) with CH3Br/HCOOH
and degradation of the sulfonium salt in aqueous N a H C 0 3
solution (yield 75 %)I2].
N
I
CONHCH,
Received. October I . 1975 [ Z 331 I € ]
German \errion' A n g e u Chem. KX. 54 (1976)
CAS Registry numbers:
( / I . 53941-82-5: / a / . 57620-58-3: i Z h i . 57620-59-4: 17cI. 57620-60-7:
methanethiol. 74931
Amino Acids and Peptides, Part lB.-.--Part 17: ref. 121. -Also: Dehydro
Amino Acids, Part S.-Part 4: ref. [ 2 ] .
121 E . dhier and d' Slhinirlr, Chem. Ber . in press.
[3] a) E . G P O S SH. . H. Kilrz, and E. Nebdin. Hoppe-Seylers Z. Physiol.
Chem. 354. 799 (1973): b) E. Gross. Intra-Sci. Chem. Rep. 5, 405 (197 I ).
[4] M . SoLolodj.. 7. Sudeh, and A. Putchorriik. J. Am. Chcm. Soc. 86.
1212 (1964).
[I]
Synthesis of Phosphorus Ylides at a Cobalt-Complex
Center[**]
By Hans-Friedrich Klein and Reinhard Hammerl*l
During oxidative additions to tetrakis(trimethy1phosphane)cobalt(o)['] the electronic configuration of the metal changes
from d 9 to d Y ;this results in a 2 : 1 stoichiometry for such
reactions in accordance with Eq. (1).
CONHCH,
CH~S@/TH,SH
2 L*Co
,-
+ x-Y
L = (CH3)3P
-
L,CoX
x=
+
L,COY
+
L
(1)
€1, Y = C l
X = CH, 1'1, Y = B r
ill
Z
=
C,Hs-CHZ-O-CO
120)
We have found that the addition of 1,l-dihaloalkanes in
the sense of Eq. (1) [ e . g X=RCHCI, Y=CI] does not stop
at the stage of the haloalkylcobalt(r) complex, but proceeds
with 3:2 stoichiometry in accordance with Eq. (2) to give
a complex cobalt dihalide having two ylidic alkylenetrimethylphosphorane ligands
I+ 15% 12b) 1
Compound ( 2 a ) and the diastereomeric L-cysteinyl derivative ( 2 6 ) can be distinguished on the basis of the chemical
shifts of the S-methyl and N-methyl protons in the NMR
spectrum [ ( 2 a ) , 6=2.10 (s), 2.67 (d); ( 2 b ) , F=2.14 (s), 2.62
(d) (both 100 MHz, in CDCl,, TMS internal standard)]. ( 2 b )
was obtained in 68 "/o yield from Z-L-Cys(SMe)-OH and L-HPro-NHCH, by the DCC'method[21,m. p. 127--130°C (from
- 8 4 ' (c = 1.096 in CHCI,).
ethyl acetate), [CX]:"
In order to establish the configuration of (2) beyond doubt
we prepared the enantiomer N-benzyloxycarbonyl-S-methylL-cysteinyl-D-prolinemethylamide(2 c) in 64 "/, yield from
Z-L-Cys(SMe)-OH and D-H-Pro-NHCH, by the DCC
method; m.p. 112-113'C
(from ethyl acetatelether),
[a];"= +S4" (c=1.094 in CHCI,). The enantiomer proved
to be identical with ( 2 a ) , except for the opposite sign of
rotation.
N - Benz~~lox~.carbonyl-S-meth~.l-~-cysteinyl-~~-pro1ir~emethplamide ( 2 a )
A solution ofNaOC,H ( 3 mmo1)and methanethiol(500mg)
in anhydrous ethanol (4ml) is added to a solution of ( I )
(330mg, 1 mmol) in anhydrous ethanol (4ml) and the mixture
stirred for 2 h. The ethanol is then removed under vacuum,
and the residue taken up in dichloromethane (20ml) and
washed twice with H,O (2x3ml). The CH,CI, solution is
dried over Na,SO,, evaporated under vacuum, and the oily
9
In this reaction a chlorinu~fiuecarbene is formally transferred and not a chlorocarbene as in the Wittig reaction''!
( I ) has a magnetic moment ( ~ ~ ' 2 6 . 3x 10-6gcm-3;
p'ert=4.39pB),which is in good agreement with that of the
jsoelectronic [(CH,),PO] ,CoCI 2 [ 6 ! As shown by the IR spectrum on reaction with CD,CI, deuterium is distributed over
all C atoms of (2).
It seems plausible that the overall reaction proceeds in
three steps:
~
[*I
[*] ProT. Dr. U. Schmidt and Dr. E. Ohler
Organisch-Chemisches Institut der Universitat
A-1090 Wien. Wahringer Strasse 38 (Austria)
p*]This work was supported by the University of Vienna Jubilee Fund.
.I
4L
Univ.-Doz. Dr. H.-F. Klein and DiplLChem. R. Hammer
Anorganisch-chemisches Institiit der Technischen Universitst
8 Munchen 2 , Arcisstr. 21 (Germany)
This work was supported by the Deutsche Forschungsgeineinschaft
and the Fonds der Chemischen Indiistrie.
[**I
A n g n v . Chon l n i . Ed. E n ( / / . 1 Vid.
I 5 11976) No. I
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induction, optical, formation, cysteine, biomimetic
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