Note: Descriptions are shown in the official language in which they were submitted.
~ i~ 7 ~
Asymmetrically sub~tituted diaminodicarboxylic acid - f -~
derivativQs and a process for th~ir preparation.
The invention relates to novel asymmetrically
substituted diaminodicarboxylic acid derivati~e~ a~d a
process for their preparation.
A~ymmetrically Rub~tituted diaminodicarboxylic
acid derivative~ are useful interm~diate~ for the
syntheRi~ of peptid~.
In J. Org. Chem. 1980, 45, 3078-3080,
a~ymmetrically substltuted diaminosuberic acid deriva-
ti~ are describ9d which were prepared by mixed Rolbe
synthe~i~. Separation of the symmetrical by-product~ was
unsucce~f~l thsre. The preparation of a~ymmetrically
~ub~tituted diaminopimelic acid deri~ati~e~ by a compli-
cated 9-stage enantio~elective synthe3is iB al~o known
from Tetrahedro~ Lott. 30, 1982, 33, 4727-4730.
~nexp~ctedly, it ha~ been po~sibl~ to find ~ovel ~ -
a~ymmetrically substituted diaminodicarboxylic acid
derivativec which are u~ful i~tQrmcd~ate~ for the
~ynthe~is of peptide~ a~d co~pou~ds containing un~atural
~mino acid~.
The in~ention thereore relate~ to a~y~metrically
sub~tituted diaminodicarboxylic acid deri~ativ~a of the
formula
O O
Il 11
A - C - CH - (C~2 )n ~ CF.' - C - }~ (I) ....
E-NH F-NH
25 in which
A and B i~d~pende~tly oi o~e a~otker i~ each,ca~e
denote a radical -OR where R de~otes an optionally mono-
or polyhalogenated ~traight-chain, bra~ched or cyclic
alkyl radical having 1-10 C-a~o~s, phe~yl ox the radical
-CH2-X, where X de~otea the radicals 9-~luoren~l, phenyl,
-OC~3~ -C~2SO2C$3, ~C~2So2C6~s~ -CC13~ C~2-Y, with Y
denoting halogen, -p-to~yl, a phenyl or phenacyl radical
't~ r~g
which ia op~ion~lly mono- or poly~ub~tituted by halogen,
N2 or alkoxy, diph~ylmethyl, triphenylmethyl,
2-pyridyl or a radical SiR1R2R3, where the radicals R1, R2
and R3 in each ca~e independently of o~e another can
denote a ~traight-chain or branched alkyrl radical having
1-4 C atom~ or phenyl,
E and F in each ca~ denote an optionally
halogenated ~traight-chain, branched or cyclic alkyl
radical havin~ 1-10 C atom~ or a radical
0~ o,W
wh~re W can d~note a 9-fluoreny~meth~l radical or a
benzyl radical which i~ optionally mono- or
poly~ub~tituted by halogen, -~0~, alkoxy or -CN or mlxed
radiaals there~rom, or the ~ubntituent~ E a~d F, i~ th~
hydrog~n atom i~ omitted, togeShQ~ with th~ nitrogen atom
form one of the foll~wing ri~g ~yst~m~
~N Csl ~N
where, lf the radicals A and B are diff~rent, ~ and F can
be different or identical, on the oth~r hand if ~he
radicals A and B ar~ ident~al, E a~d F ~u~t be
dif4erent,
and n denote~ an integer ~rom 2 to 10, wh~re the center~
of chirality in the moleaule~ are dekermined by the
~tarting material~ u~ed and both c~n have th~ L
co~iguration or both can hava the D or D,L or L,D
configuzation resp0cti~ely.
The invention further relate~ to a proceR~ for
the prepara~ion o~ such asymmatrically ~ub~titut~d
diaminodicarboxylic acid derivativa~ by mixed g~lbe
l - :
-- 3
~ynthe~i~, which i8 characterized in that a protected
amino acid deri~ati~e o~ the ~ormula
O
A - C - C~ - (CH2)k - COOH (Il)
E-NH
in whlch A and E have the abov~tioned m~aning and k
denote~ a~ integer,
i8 ~ub; octed to electrolysi~ on plati~u~ wire-gauzo
elec~rode~ with an d ~o acid derivative o~ the formula ~ ~
O : . .-.:
E~OOC - (C~2)1 - C~ - C - B ( 111 )
F-~ :
in which B and F haYe the abov~m0ntio~ed meaning a~d 1 ~:
denote~ an integor, where k and 1 together make the
number ~.
In the ~ormulae I, II a~d III, A and ~ in each
ca~e denote the radical -OR, where R denotes ~n
optio~ally mono- ox polyhalogenated ~traig~t-cha~n or
branched or cyclic al~yl r~dical having 1-10 C atom~, for
example an optionally halogenated methyl, sthyl,
15 i-propyl, n-butyl, i-butyl, t-butyl radical a~d the like, : ::
a cyclohexyl, cyclopentyl or cyclobutyl radi~al Qr
phe~1.
R can additionally denote the radical -C~-X,
where X denote~ the radical~ 9-~l~orenyl-, phenyl-,
-OC~I3~ -CH2SOlC~3~ C~aS02CCHs~ -CC~3~ -C~2-Y, llqith Y
denoting halogen, -p-to~yl, a ~henyl or phenacyl radical
which i~ optionally mono- or poly~ub~tituted by halogen,
-NO2 or alkoxy, or exampl~ p-bro~ophenacyl,
p-chlorop~e~acyl a~d the like,
diphenylmethyl, triphenylmethyl, 2-pyridyl, or a radical
-SiR~R2~, wh~re the radical~ Rl, R2 and R3 in ~aah ca~e
indepe~dently of one another can denote a ~traight-ch~in
or branched al~yl radical haYing 1-~ C atom~ or phenyl.
,~. .. ,~ . :,:
, . .,. . ., . " ,:
i;,: ~ . . . . ; :
~,.j, ., ~ ~ ,
,": : .
: . : , ,
3 ~ 3
-- 4
Preferably A and B d~note a radical -OR, where R
denote3 a 9-fluorenylmsthyl or a sub~tituted or unsub~ti-
tuted phenyl, be~z~l or phanaeyl radieal or an optionally
h~logenated ~t~aight-ehain or branehed al~yl radieal
ha~ing 1-4 C a om~.
The radieals ~ and F in eaah ca~e denotQ an
optio~ally halogenated straight-ehain, branehed or eyclic
alkyl radieal having 1-10 C atom~, ~or example a methyl,
ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl,
p~ntyl or hexyl radieal and the like, which ean optio-
nally be mono- or polyhalog~uated.
The xadieals E and F ean additionally denote a
radieal
o o
~ or ~ O,w
where W denotes a 9-fluoronyl~thyl radieal or a b~nzyl
radieal whieh i~ optionally mo~o- or ~olysubstituted by
halogen, ~2~ alXoxy or -C~ or mixed radieal~ therefrom,
for example a bromobenzyl, dlbromobenzyl~ chlorobenzyl,
diehlorobenzyl, nitrobenzyl, methoxyben~yl or eyanobenzyl
20 radical aud the liks. ~.
The ~ub~titue~t~ E and F, i~ the hydrogen ato~ i8
omitted, can additionally form one of the ring ~y~tems
indicatsd.
The radical~ E and F preferably in each case
denote a radical
o o
~ w or ~ O,~
where W denotes a 9-fluorenylmethyl radical, an op~io-
~ally sub~tituted benzyl radical or a ~traight-chai~ or
branehed alkyl radical ha~ing 1-4 C ato~.
If the radical~ A a~d ~ are difierent, the
~ub~tituent~ on the amino functio~ of the dicarboxylic
acid can be identical or differsnt. I the radlcals A and
B ars identical, the sub~tituents on the amino function
. . ., ~ -:. , . :
3 ~
-- 5
of the dicarboxyllc a~id mu~t b~ di~fer~nt.
The cent~r~ o chirality o~ the dicarboxylic
acids are determin~d by the ahoice o the starting
materials used. They c~n either both have the D aonfigu-
ration or both have the L or D,L or ~,D configurationrespectively, for axample N'-E-N''-F~ D,L-
2,7-diaminosuberic acid mono-A e~ter mo~o-B e~ter when
u~ing N-~-D-glutamic acid A ester and N-F-~-glut~mic acid
B ~ster.
The a~ymmetrically ~ubHtituted dicarboxylic aaid
dQr~vati~s according to the in~ention can be prepared by
mixed ~olbe syn~h0~
In this proc~a~, appropri~taly protectQd amino aci.d
derivati~s~ are ~ubjected to elactroly~is on platinu~
wire-gauze elect~odes.
The ~tarting compow~d~ are known from the literature or
can be prepared by ~ethods ~amlliar to the per~o~ ~killed - -
i~ the art.
The amino acid d~rivative~ are di~olved in a
20 801ve~t which i~ inert under the reaction condi~lo~u.
Suitable ~olvents are, for example, lower aliphatic
alcohols, for example methanol, ethanol, propanol or
i-propanol er a heterocyclic ~olvant such a~, for
exam~le, pyridine, or dimethylformEmide, aceto~itril~,
nitromethans or ~ixtures of such ~olv~t~.
In the electroly~ ell the ~olution o~ a ba~e
i~ added, 40r e~mplQ alkali metal in alcoholic ~olution~ -
for ~xample ~odium methoxide in methanol~ or pot~sium
ethoxide i~ ethanol.
Electrolysi~ is then carried out on platinum
wire-gauze electrode~ with cooling, the t~mperature
preferably being kept at 18-25C. The current stre~gth
during th~ electroly~is is about 5-15 A at 60-120 V
applied ~oltage a~d i~ otherwi~e independ~nt of the
geometry of the Qlectrode~ used.
The electrolysis proce~s i~ compl~e as ~oon as ~tarti~g
material can no longer be de~er~ined in the electroly~is
solution .
The electroly~i~ solution i8 th~n option~lly concen ~ated
.:.:, :: - ~ ,, - , ' , '
~, . :- . , . :: ,
f,J 7 ~
-- 6
under low pre~ure, the residue i~ taken up ln a suitable
~olvent, for example ethyl acetate, and thi~ solution iB
wa~hed succe~nlvely with dllute acid, for exa~ple dilute
hydrochloric-acid, a saturated ~alt ~olution, for example
a ~aturated ~odium hydrogen carbonate ~olutio~, a~d
saturatsd ~odium chlorida nolution.
The ~olution i~ then dried with a ~uitable drying agent,
for example ~odium nul~ate or magnesium uul~ate, filtered
and concentrated agai~, optioually under low prea~ure.
The redidue i~ purif ted by chromatography, for
example on silica gel, it being po~sible to separate the
~ymmetrically cub~t~tuted by-product~. The reaction
proceed~ in a good yield of 10-15 % of theory to give the
de~ired a~ymmetrically ~ub~tituted ~inal product.
15 ~xample 1: :~
29.41 g (96 mmol) o~ ~-t-butyl N-t-butoxy~
carbonylgluta~ate and 35.63 g ~95 ~ol) of ~-benzyl N-
benzyloxyaarbonylglutamate were dis~ol~ed i~ 240 ml of ~ -
MeOH and 80 ml of pyridin~ by ~wirli~g. The reaction
20 ~olutio~ wa~ tran~ferred to the electroly~i~ cell haviug ~ ~:
cylindrically arranged plati~um wire~gauze electrode~. It
was rinsed with MeO~ and the electrolysi~ cell filled
with MeOH until both el~ctrode3 wer~ compl~tely i~mersed.
o.a ml of NaOC~3 (30 % in MeO~) wa~ then added, and the
25 electroly~i~ c911 wa~ well cooled. When the reaction :
801utlon ha~ cooled to 15C, ths wire-gauze apparatu~ i~
~witched on. The reaction temperature wa~ kept b~tween
~18 and +24C by temperature contro~ or by con~rol o~
the current strength or curre~t potantial (5-15 A, 60- -
120 V).
The ~eaction cour~e wan checked by ~eans of T~C.
After complete reaction the reaction ~ol~tio~ wa~ ao~c~n ;:
trated in a rotary evapor3tor at 40C.
The res~duQ ~rom the Kolbe ~ynthesi~ was
dis~olved in 500 ml of ethyl a~etate, and wa~hed ~ t
with dilute ~Cl ~olutlon (25 ~1 o~ conc. ~Cl made up ~o
250 ml with H20), the~ with 250 ml o~ ~at. NaHCO3 and
,.,. , . , . " .. , - ~ . . . ~ -
: ::;: . , : , .
, . ~ , ,, . .: . , - , :
, .. , .,, - . . . .
: , . . .
Y~ 3
finally with 250 ml e~ch of ~at. NaCl up to neutrality of ~ ;:
the aqueous pha~e.
The organic phase wac dried with Na2SO~, fi~tered
off and evaporated~
~vaporation re idue: 58.17 g.
The evaporatio~ re~idue wa~ ~iltered through
silica gel and then ~eparated by ~eianc of ~PLC.
Yield: 4.5 g of pure mo~obenzyl mono-t-butyl
N'-benzyloxycarbonyl-N''~t-butoxycarbo~yl-2,7-diamino-
suberate (10 ~ of theory), m.p. 51-56C, 1~]D = -21.5.
The following compoundR were prepared in a~ ~ ~-
analogou~ ~anner:
i ~ - ~ =
No _ ~3 F n
2 0-benzyl 0-methylt-butoxycarbonyl t-butoxycarbonyl 4
1 5 3 0-benzyl 0-benzylt-butoxycarbonyl b~nzyloxyearbonyl 4
, ~ _
4 0-benzyl 0-2-tosylethylt-butoxyearbonyl benzyloxyearbonyl 4 : :
_ . . "::
0-benzyl 0-2 to~ylethylt-butoxyearbonyl t-butoxyaarbonyl 4
l _
6 0-benzyl 0-2-to~ylethylt-butoxyearbonyl benzyloxyearbonyl 3
I_ __ _ ' ' :~:
7 0-benzyl 0-2-to~ylet~ylt-butoxyearbonyl benzyloxyearbonyl 2
I _ _ ~ ~ ' ~
2 0 8 0-benzyl 0-methylt-butoxyearbonyl benzyloxycarbonyl 3 . ~
l_ _ _ : ' : '
9 0-benzyl 0-phenaeylt-butoxycarbonyl benzyloxycarbonyl 3 ~ :~
I_ . _ . _ , ~, ,
0-benzyl 0-2-trimethyl-t-butoxycarbonyl benzyloxycarbonyl 3
isilylethyl
l _
11 0-benzyl 0-benzylt-butoxyci~rbonyl benzyloxyearbonyl 3
_ _
12 0-benzyl 0-2,2,2-trl- t-butoxycarbonyl benzyloxycarbonyl 2
chloroethyl _
2 5 13 0-benzyl 0-benzyl t-bu~oxycarbonyl benzyloxycarbonyl 2 I _ _ _ _ _
14 0-benzyl 0-2-tosylethyl t-butoxycarbonyl benzyloxycarbonyl 3
I _ _ . _ _ _
In ~xample~ S a~d 14 the corre~ponding D- and L-
amino acid deri~ati~e~ were employed in mixed ~orm.
Chemical data of the abo~ementioned compound~, where the
abbreviation~ u~ed havs the following meaning:
...... - , ....... .. . . . .
,., . , . , ,. . .: ..................... .::. :
, : . , - ~ :- ~ ::: . : ,
3 i~
.
Abbrsviation ~eaning
_ _
OBn O-benzyl
I _
O~e O-methyl
I _ _
OEtTo~ O-ethyltosyl
I _
OtBu O-tert-butyl
I _ .
Boc t-butoxycarbonyl
_ _ .
Z benzyloxycarbonyl
~ .
SlJ~3 r~=4
l : :
¦PIM n=3
ADI n=2
I _ _
Examl~le_1: Boc-Z-Sl~B-OtBu-OBn ~ 6
13C-NMR(CDCl3, 100 M~z): 24.80~C~2), 24.82(C~Hl~, 28.02(0-t-
l3u-CEI33, 28.34SBoc-C~I3), 32.52(C~a), 32.72(CEl2), 53~82(C~I)o
67.00 and 67.12(benzyl-l~I2), 79.62( (C}I3) 3C~ of Boc),
15 81.57( ~CH3)3C of OtBu), 128.09-128.63(aromatic C), 135.36,
136.30, 155.34 and 155.87(carbamate CO), 171.86 and ~ ~ -
172.22 (CO) O
Mp. 51-56C
= -21.S
: .
20 Example 2: Di-Boc-S~-OBn-O~e
~3C-NMR(s~DC13~ lOOMH~): 24.82 (2CH2) ~ 28.31 (CH3)3C),
32.49(CE2), 32.54(CH2), 52.18(0CH3), 53.38(br ~3, 2CE~), -
66.99(benzyl-CH2), 128.31, 128.42, 128.59, 135.46, and
155.32(2 carbamate-CO), 172.57 and 172.20(euter CO).
M.p. 55-59C
~a:lD= -24.9 (1 % in DMF)
Exa~pl~ 3: Boc-Z-SlJB-Di-OBn
~3C-NMR(CDCl3, lOOMHz): 24.68(CH2),24.81(CH2),
28.32(2 (CEI3)3C), 32.4712C~I2), 53.37(C~I), 53.83(C~),
66.99(benzyl-CH2), 67.13(be~3Yl-C~2)~ 79.90((C~I3)3C),
128.10-128.63 (aro~atic C), 135.33, 135.46, 136.28, 155.30
., .. ~ ., , , . ., ~ , . . .
. . .: . :. : : : - . . . : . . ~ . . ,
,.. ~ .. ,, . ., " , . . , : . . ,
~' ,'' ,'' '' . '' "' ` ~ ' ` ' : ., '' . '
'1, ' : ,'' ' ~ . . ~ ' ' ' ' ''
'' ' ' ~',: ' ' ' ' ' ' ~'.' '
,~, ' '' ' ' ' : ". . :
".' ,'' ' ' , .'i ' ' ~ ' .' ,
and 155.83(Carbamat~ CO), 172.17 and 172.56(e~ter CO)
M.p. 65-67C
[~] D = 1 . 4 (5 % i~ C~ICl3)
EXamP1~ 4: BO~-Z-S~B-OBn- OE tTOB
l3C-N~R(C~Cl3, 1001~Iz): 21.65(tolyl-CH3), 24.65(CH2)~
24.81(CEI2), 28.32((~I3)3C)~ 32.06 (C1E~2) ~ 32.38(CH2),
53 .12 (CH), 53. 80 (CEE), 54.94 (OCEIlC~2SO2C.~E7),
58. 27 (OC~I2CHaSO2C7H7), 67.01 (beIlzyl-cH2), 67~17(benzyl-C~2),
80.05((C~I3)3C), 128.12~128.65(arOma'CiC C), 130.08, 135.32,
10 136.27, 145.23, 155.26 a~d 155.90 (carbamate CO),
172O15(2 ~8ter CO)
Oil
[a~] D +3.45 (5 % in ~}ICl3)
Example 5: Di-Boc-D,I.-SllB-OBn-OEtTo~
lS l3C_NMR(CDCl3~ 100MEIz): 21.63~tolyl-C~I3), 24.79(C~
24.84 (C~1:2), 28,31(2 (C~3)3C) ~ ~2.13 (C~EI2), 32.5~(C~2),
53.23(br ~, 2C~), 54-99(C~2C~a92C7H7)~
5828(C~ 2S2C7}I7), 6701 (benzyl-CH2), 79.98(2(CE3) 3C),
128.13-128.61(arOmatiC C), 135.45, 136.35, 145.21, 155.30
20 and 155.83(carbamate CO), 1'72.11(2 e~ter CO)
Exam~le 6: B~C-Z-PIN-OBn-O~tTOB
3C-NMR~COCl3, lOOMElz): 2~L.lO(C~2), 21.60(tolyl-CEI3),
28.31((CH3)3C), 31-62(CH2)~ 31.90(CH2), 52 85(CH)~
53.55(C~), 54.93(O~H2C~2SO2C7~7), 58~32(OC~2G~2SO2C7~7),
25 67.05 and 67.22(benzYl-CH2)~ 80-08((CE~3)3C)~ 128-11-
128.66(arOmatiC C), 130.05, 135.31, 136.25, 145.21,
155.45 and 155.83(carbamate CO), 171.97 and 172.08 (e~ter
CO)
EXamP1e 7: BOC-Z-~DI-OBn-OB~TO~;
30 13C_NMR$CDC13, 100M~Z): 21.60(tO1Y1-CH3)~ 28.17((CH3)3C~,
28.29(C~2), 52.795CH), 53.61(CH), 54.87(OC~3CH2~O2C7~7),
58-29(CH2C~S2C7~7)~ 67.04 ;3nd 67~31~benZY1-C~2)~
80.18((CH3)3C1,128.05-128.67(arOmatiC C), 130.09, 135.24,
136.20, 136.26, 145.27 a~d 156.00(2 Ca~bamate CO), 171.59
and 171.75(e~t~r CO)
,1 cJ ~
- 10 -
Exam~e 8: Boc-Z-PIPq-OBn-OP~3
3C~ CDCl3~ 100MHz): 20.82(CH2), 21.16~C~2)~
28.31((CH3) 3C) ~ 31.97(CHl), 32.17 (C~2) ~ 52.23(0~
52.93(C~), 53.61(C~I), 67.07(benzyl-CH2), 80.01((C~I3)3C),
128.17-128.64(aromatic C~, 135.29, 136.23, 155.55 and
156.06(carbamate CO), 172.12 and 173.06(e~ter CO)
Exam~le 9: Boc-Z-PIP~-OBn~ IaCOC~5
R(cDcl3~ 100P~z) 20.82(2CH~), 28.33((~3)3C),
31.86(CH2), 32.16(CH2), 53~08(CH), 53.69(C~
66.35(O~I2COC6~Is), 66.97(benzyl-CEIa), 67.13(be~zyl ~EIa3,
80.05~ 13~3C), 127.77-128.89(axomatic: C), 133.99, 135.43,
136.36, 15S.Sl and 156.17lcarbamate CO), 172.16(2 e~ter
CO)~ 191.61(OC}I2~:OC6E~5)
E:xample 10_ Boc-Z-PI~ t)BY~ ~Si~C~3)3
s3C-NMR(d6-DMSO~ 100MHz): -1.54 ( (C~3)3Si),
17.42 (OC~,CE~2Si (C~I3)3), 21 ~22 (C~2) ~ 22 o2S) (CE~2)
28 ~ 32 ((~}I3)3C~, 31.91(C~,), 32.34(C~Ia), 53.01(C~
53.73(C~I), 63.74(0~I2C~Si ~C~EI3) 3), 67.05~be~lzYl-(~2)~
67.17tbenzyl-C~2), 79~89((CHI)3C)~ 128~14~ 128~26~ 128~50
128~64~ 135.32, 136.25, 155.58 alld 155.06(carbamate CO),
172~17 and 172~68 (2 ester CO) ;
Exam~l~ 11: Boc-Z-PI~-Di-OBn
3C_NMR(CDCl3~ 100MEIz): 21.14(CH2), 28.30((~II)3C),
31. 92 (CHa), 32.16(CH2), 53.07(ClI)~ 53 ~ 64(CH), 67 ~ 06 (2
benzyl-C }Ia), 67.18(benzyl-CEI2), 79.98((C}I3)3C), 128.16,
128.29, 128~44~ 128~50~ 128.61, 128.63, 135~30~ 135~40~
136.24, 155.53 and 156.04(carbamate CO), 172.09 and
172.41(2 ester CO).
Exam~le 12: ~oc-Z-BDI-OBII-OOElaCCl3
~3C-N~R~CDC13, 1001~EIz): 28.60((C~3)3C), 29.25~C~2)J
30.00(CH2), 53.34(C~I), 53.78(C~1), 74.67(O~I2CCl3),
67.47(beDzYl-c~2)~ 67.72(b~nzyl-CH2), 74.67(0C:HlCCl3),
80.69((C~I3)3C), 94.79~0C~I2~Cl3), 128.4~, 128.54, 128.74,
128.87, 128.96, 129.02, 135.43, 136.46, 155.53 z~nd
156.17(carbamate CO), 171.09 and 171.96(2 CO)
: . ~ . ~ . . . . . ~
:, ~ ~ : , ., . . , , .,:
h'$ ~ 79~S
11
~xample 13: ~oc-Z-ADI-Di-OB~
R(cDcl3~ 100M~z~: 21.22( OEl)~22.20(CH23,
28.32( (C~3) 3C), 31.91(CH2), 32.34(CH2~, 53.01(CH),
53.73(CH), 63.74(OCH2CH2Si (CH3) 3), 67.05(b~nzyl-C~2),
67.17(benzyl- ~ ), 79.89((CH3)3C), 128.14, 128.26, 128.50,
128.64, 135.32, 136.25, 155.58 and 156.06(carba~ate CO),
172.17 and 172.68(2 e~ter CO).
ExamDle 14: Boc-Z-D,~-PI~2-O~n-OEtTo~
~C-~MR(CDCl3, 100N~z)s 20.98(CH2), 21.58(tolyl-CH3),
28.29(CH3)3C), 31.77(C~), 31.93(CK2)~ 520g~(C~
53.73(C~), 54.94(OCK2~2SQ2~E~), 58.25(OC~C~2SO2C7~7),
67.00 a~ 67.15(~enzyl-~23, 80.10((C~333C), 128.09-
128.64(aromatic C), 130.05, 135.31, 136.32, 145.19,
155.28 and 156.02(carba~ate CO), 171.87 and 171.94(Q~t~r
CO~
