2-O-benzylation in D-gluconamide derivative under basic conditions with complete retention of stereo-integrity: Convenient access to 2-O-benzyl-3,4:5,6-di-O-isopropylidene-D-glucitol and other differently protected D-glucitol derivatives

Article abstract of DOI:10.1080/07328300902979503

A new and convenient synthesis of 2-O-benzyl-3, 4: 5, 6-di-O- isopropylidene-D-glucitol has been accomplished and has been generalized with the syntheses of differently protected D-glucitols at C-2 position. In the course of our new route to the different

Full text of DOI:10.1080/07328300902979503

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2-O-Benzylation in D-Gluconamide
Derivative Under Basic Conditions
with Complete Retention of Stereo-
Integrity: Convenient Access to 2-O-
benzyl-3,4:5,6- di-O-isopropylidene-D-
glucitol and other Differently Protected
D-glucitol Derivatives
B. N. Manjunath a , K. Harikrishna a , Indrapal Singh Aidhen a & B.
Varghese b
a Department of Chemistry , Indian Institute of Technology Madras ,
Chennai, 600036
b Sophisticated Analytical Instrument Facility , IIT-Madras , Chennai,
600036
Published online: 06 Jul 2009.
To cite this article: B. N. Manjunath , K. Harikrishna , Indrapal Singh Aidhen & B. Varghese (2009)
2-O-Benzylation in D-Gluconamide Derivative Under Basic Conditions with Complete Retention of
Stereo-Integrity: Convenient Access to 2-O-benzyl-3,4:5,6- di-O-isopropylidene-D-glucitol and other
Differently Protected D-glucitol Derivatives, Journal of Carbohydrate Chemistry, 28:5, 264-277, DOI:
10.1080/07328300902979503
To link to this article: http://dx.doi.org/10.1080/07328300902979503
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Journal of Carbohydrate Chemistry, 28:264–277, 2009
ꢀC
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328300902979503
2-O-Benzylation in
D-Gluconamide Derivative
Under Basic Conditions with
Complete Retention of
Stereo-Integrity: Convenient
Access to 2-O-benzyl-3,4:5,6-
di-O-isopropylidene-D-glucitol
and other Differently Protected
D-glucitol Derivatives
B.N. Manjunath,1 K. Harikrishna,1 Indrapal Singh Aidhen,1
and B. Varghese2
1Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036
2Sophisticated Analytical Instrument Facility, IIT-Madras, Chennai 600036
A new and convenient synthesis of 2-O-benzyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol
has been accomplished and has been generalized with the syntheses of differently
protected D-glucitols at C-2 position. In the course of our new route to the differ-
ently protected D-glucitols at C-2 position, a new D-gluco configured building block,
1-morpholino-(3, 4: 5, 6-di-O-isopropylidene)-D-gluconamide has been achieved.
Keywords D-gluconolactone, morpholine, D-gluconamide, D-glucitol
2-O-benzyl and D-gluco-configured acyclic aldehyde 1 has served as a key
building block during the synthesis of a new conformationally constrained
2,7-anhydrosialic acid derivative,[1] through the imine 2. Due to the diverse
and significant biological roles played by sialic acids,[2] conformationally rigid
Received February 10, 2009; accepted April 16, 2009.
Address correspondence to Indrapal Singh Aidhen, Department of Chemistry, Indian
Institute of Technology, Madras Chennai 600036. E-mail: isingh@iitm.ac.in
264

2-O-Benzylation in D-Gluconamide Derivative
265
O
O
O
O
X
O
O
OH
H
O
OBn
O
OBn
1 X = O
2 X = NBn
3a
Figure 1: 2-O-benzyl glucitol derivative 3a—A precursor of valuable intermediates 1 and 2.
structures[3,4] have been very attractive and important synthetic targets.
These have served as valuable tools for the investigation of biological ques-
tions. Although aldehyde 1 is conveniently obtained by oxidation of 3a using
Dess-Martin reagent, it is the ready availability of 3a that is more crucial and
important.
Our three-step protocol[5] constituting conversion of D-glucono-lactone
4 to α-hydroxy-methyl ester 5 by a known method[6] and subsequent
2-O-benzylation under nonbasic conditions, followed by reduction with lithium
aluminum hydride, continues to remain the only reported procedure in the
literature. It has been used by Yao[1] to arrive at alcohol 3a (Sch. 1 ). Our
subsequent experience has shown that the O-benzylation using Ag2O/BnBr
is not free of difficulties. On a smaller scale (1 mmol), the reaction was sat-
isfactory; however, the conversion always remained incomplete, despite long
hours of reaction time, when conducted on a scale greater than 1 mmol. Even
with excess equivalents of Ag2O/BnBr and a change of solvents, isolated yields
of 6 did not improve to more than 45% after careful and tedious silica gel
column chromatography. Confronted by this difficulty and the immediate need
of glucitol derivative 3a as a chiral building block for other synthetic targets
in our group, we searched for a convenient alternative. Presented herein are
the results that not only provided an efficient synthesis of 3a on multigram
scale, but also paved the way for a general high-yielding route to differently
protected glucitol derivatives 3b–i. The alternative procedure starts with
1,2:3,4:5,6-tri-O-isopropylidene-D-gluconate 7, conveniently available on a
multigram scale in a single step from D-gluconolactone by a procedure at-
tributed to Jarosz.[7] Lactone 7 on heating with morpholine in toluene at 90◦C
furnished a hitherto unknown α-hydroxy morpholine amide 8 in an isolated
yield of 95% as a solid (Sch. 1).
The α-hydroxy amide 8 was subjected to O-benzylation using sodium
hydride as base and in anhydrous DMF at room temperature. A clean reaction
ensued in 30 min, giving the α-O-benzyl amide 9a in an isolated yield of 90%.
Since 2-O-benzylation has been done under basic conditions using sodium
hydride, all associated apprehensions of any tampering of the stereochemistry
at C-2 center were completely alleviated by comparing the product obtained
through the benzylation of α-hydroxy amide 8 to that of the product obtained

B.N. Manjunath et al.
266
O
O
O
O
OMe
O
OR1
c
a
5: R1 = H
6: R2 = Bn
b
OH
O
O
O
HO
O
HO
OH
OH
O
O
OBn
4
3a
d
g
O
O
O
O
O
O
O
O
N
e
O
O
O
f
OR2
O
O
8: R2 = H
9a: R2 = Bn
7
Reagents and conditions:
(a) Reference [6]; (b) Ag2O (2eq.), BnBr (1.1eq.), CH2Cl2, rt, 48h, 45%;
(c) NaBH4 (1.5 eq.), MeOH, rt, 12h, 90%; (d) Reference [7];
(e) Morpholine (4eq.), toluene, 90°C, 18h, 95%;
(f) NaH (1.1eq.), BnBr (1.1eq.), DMF, 0°C-rt, 30min, 90% or Ag2O, BnBr, CH2Cl2, rt,
48h, 50%;
(g) NaBH4 (10eq.), EtOH, 60°C, 12h, 86%.
Scheme 1. Synthesis of 2-O-benzyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol 3a.
using a combination of silver oxide and benzyl bromide. The products obtained
by either of the methods matched extremely well in optical rotation and
their IR spectra were completely superimposable in the fingerprint region.
The amide 9a further underwent clean reduction with sodium borohydride
in ethanol at 60◦C, furnishing the 2-O-benzyl glucitol derivative 3a in an
isolated yield of 86%. The optical rotation and spectral data of the obtained
material perfectly matched with that obtained through the conversion 6 → 3a
using lithium aluminium hydride as reported earlier[5] or using sodium
borohydride. This further unambiguously proved the complete retention of
the stereochemistry at the C-2 position in the amide while affecting the O-
benzylation reaction under basic conditions. The convenience in using NaBH4
for the reduction of the amide 9a to glucitol 3a, as opposed to the use of
LiAlH4 for the conversion 6 → 3a, offered a significant advantage to this alter-
native preparative procedure for 3a. The conversion of α-hydroxy amide 8 to
2-O-benzyl-protected glucitol derivative 3a has been generalized, and this has
enabled incorporation of other protecting groups at the C-2 hydroxy (Table 1).
The convenient availability of 2-O-benzyl morpholine amide 9a, a crys-
talline solid with an indefinite shelf life, on multigram scale makes it a valu-
able building block with D-gluco configuration. Its ready conversion to differ-
ently protected D-glucitol is illustrated herein. The x-ray crystal structure data

2-O-Benzylation in D-Gluconamide Derivative
267
Table 1: Differently protected glucitol at C-2 position 3a–i
O
O
O
O
O
(b)
O
(a)
O
OH
N
8
O
OBn
O
OR
9a-i
O
3a-i
Reagents and Conditions : (a) : NaH, DMF, RX, ( X = Cl / Br / I ), 0°C - rt, 30 min.
(b) : NaBH4, EtOH, 60°C, 12h.
(%) Isolated Yield
Optical Rotation
Amide
9a–i
Glucitol
3a–i
Amide
9a–i
Glucitol
3a–i
Entry
RX
C6H5CH2Br
a
b
c
d
e
f
g
h
i
90
95
90
94
97
90
86
77
78
86
90
80
75
90
82
91
89
83
+10.79
+15.79
+16.49
+35.12
+10.19
+25.18
+6.19
+26.38
+20.58
+13.70
+12.39
+4.99
4-(MeO)-C6H4CH2Cl
3,4-(MeO)2-C6H3CH2Cl
HC≡CCH2Cl
CH2 CHCH2Br
CH3O(CH2)2OCH2Cl
CH3I
−8.39
+14.49
+22.183
+15.58
CH3CH2I
CH3CH2CH2CH2Br
+15.189
+11.99
Figure 2. ORTEP plot[8] of compound 9a with thermal ellipsoids drawn at 50% probability
level (Johnson, 1976).

B.N. Manjunath et al.
268
Table 2: Summary of crystal data and data collection parameters for
1-morpholino-(2-O-benzyl-3, 4: 5, 6-di-O-isopropylidene)-D-gluconamide (9a)
Chemical formula
Formula weight
Crystal system
C23H33NO7
435.5
Monoclinic
P 21
Space groups
Unit cell dimensions
˚
a(A)
9.7811 (6)
11.3116 (13)
11.0365 (16)
90.000(10), 99.229(7), 90.000(7)
1205.3 (2)
4
1.200
˚
b(A)
˚
c(A)
α, β, γ (◦)
3
˚
V(A)
Z
Dcalcd (mg m−3
)
Absorption coefficient µ (mm−1
F(000)
)
0.729
468
Index ranges
Crystal size (mm)
Measured data
Unique data
Parameters
0 ≤ h ≤ 11, 0 ≤ k ≤ 13, –13 ≤ l ≤ 13
0.3 × 0.2 × 0.2
2398
2277
299
Restraints
1
R (all data)
0.0454
0.1110
1.035
wR2
Goodness of fit
Mean and maximum
shift/esd
0.000, 0.000
Maximum and minimum difference
0.272 and –0.118
−3
˚
electron density (e A
)
for the crystalline solid (9a) confirmed the complete structure and retention of
stereointegrity at the C-2 position (Figure 2, Table 2). The D-gluco-configured
α-hydroxy morpholine amide 8 and the 2-O-benzyl morpholine amide 9a are
potential building blocks, which, via suitable protection/deprotection strate-
gies, can be usefully manipulated for different synthetic endeavors based on
one’s imagination and creativity.
X-RAY DIFFRACTION ANALYSIS OF 2-O-BENZYL MORPHOLINE AMIDE
9a
X-ray diffraction data for 2-O-benzyl morpholine amide 9a were collected
on an ENRAF NONIUS CAD4-F single crystal diffractometer equipped with
graphite mono-chromated Cu-Kα radiations. Unit cell parameters and orien-
tation matrix were obtained using 36 reflections collected by a random search
routine from different zones and indexed by a method of short vectors fol-
lowed by least squares refinement. The intensity data were collected by a ω-2θ
scan technique at 293◦K. Structure was solved by a direct method technique

2-O-Benzylation in D-Gluconamide Derivative
269
using the SIR92 (WINGX) program.[9] The nonhydrogen atoms were anisotrop-
ically refined. Hydrogen atoms were fixed at geometrically meaningful posi-
tions and were given riding model refinement. Full matrix least squares refine-
ment using F2 was continued until maximum shift/esd converged to zero. The
SHELXL97 (WINGX)[10] program was used for refinement. The x-ray diffrac-
tion data of compound 9a is deposited in the Cambridge Crystallographic Data
Centre (12, Union Road, Cambridge, CB2 1EZ, UK) and the data deposition
number is CCDC 719428.
ACKNOWLEDGEMENT
We thank DST New Delhi for the funding toward the 400 MHz NMR machine
to the Department of Chemistry, IIT-Madras, under the IRPHA scheme and
ESI-MS facility under the FIST program. CSIR-New Delhi is acknowledged
for funding of project 01(1971)/05/EMR-II during 2005. MBN is thankful to
UGC for Fellowship.
EXPERIMENTAL SECTION
All solvents were distilled before use. Anhydrous DMF was prepared by us-
ing standard procedures that involved drying over calcium hydride followed
by vacuum distillation. Melting points were determined in capillaries and
1
are uncorrected. H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
recorded with deuteriochloroform (CDCl3) as the solvent and tetramethyl-
silane as reference. Mass spectra were recorded on a MICRO-Q TOF mass
spectrometer by using the ESI technique at 10 eV. Optical rotations were
measured with an Autopol IV polarimeter at rt. All the reactions were mon-
itored by TLC on precoated silica gel plates. The TLC was performed and
spots were developed by dipping the silica gel plate in a solution that was
prepared by adding ammonium ceric sulfate (1 g) and ammonium molybdate
(21 g) to concentrated sulfuric acid (31 mL) and making the volume up to
500 mL with distilled water. The TLC plate was later heated to 100◦C to
develop.
Preparation of 1-morpholino-(3, 4: 5, 6-di-O-isopropylidene)-
D-gluconamide (8)
To a solution of the triacetonide 7 (5 g, 5.8 mmol) in toluene (16 mL), mor-
pholine (5.5 mL, 63.3 mmol) was added and the reaction mixture was stirred
at 90◦C for 18 h. On completion of the reaction, as monitored by thin layer
chromatography, the reaction mixture was allowed to cool and toluene was
evaporated under reduced pressure. Morpholine was removed by addition of

B.N. Manjunath et al.
270
toluene (2 × 10 mL) and distillation of the azeotropic mixture under reduced
pressure. The crude product was subjected to silica gel column chromatogra-
phy (ethyl acetate:hexane, 2:8 ) to obtain a white solid (5.2 g, 95% yield); m.p.
46–48◦C;Rf 0.16 (ethyl acetate/hexane, 4:6); [α]2D5 = –15.8 (c 1.0, CHCl3); IR
1
(neat) νmax cm−1 3430, 1650, 1371, 1247, 1213, 1112, 1063, 847, 511. H NMR
(CDCl3/TMS, 400 MHz): δ 1.26, 1.31, 1.34, 1.37 (4 × s, 12H, 4 × CH3); 3.37–
3.72 (m, 8H, morpholinyl); 3.76 (d, J = 9.2 Hz, 1H, -OH); 3.87–3.94 (m, 2H,
CH2CH); 3.95–4.14 (m, 3H, 3 × CH); 4.51 (d, J = 9.2 Hz, 1H, CHCO); 13C
NMR (CDCl3/TMS, 100 MHz): δ 26.6, 27.2, (4 × CH3); 42.9, 45.4 (2 × N-CH2);
66.3 (CH2CH); 66.4, 66.7 (2 × O-CH2); 68.0 (CH2CH); 77.1, 77.6 (2 × CH);
80.5 (CHCO); 109.6, 110.6, (2 ×CMe2); 170.3 (CO); HRMS (TOF MS ES+) m/z
[M+H]+ calcd. for C16H27NO7 345.1866, found 345.1870.
Representative Procedure for 2-O-Alkylation on the α-Hydroxy
Morpholine Amide 8
1-morpholino-(2-O-benzyl-3, 4: 5, 6-di-O-isopropylidene)- D-gluconamide (9a)
A solution of the α-hydroxy amide 8 (4 g, 11.6 mmol ) in dry DMF
(6 mL) was added to oil-free sodium hydride (0.306 g, 12.7 mmol) in DMF (1
mL) at 0◦C under inert atmosphere. This was followed by addition of benzyl
bromide (1.5 mL, 12.7 mmol) and then the reaction mixture was allowed to
stir at rt for 30 min. On completion of the reaction, as monitored by thin layer
chromatography, the product was extracted using ethyl acetate (20 mL) and
the DMF was removed by washings with brine solution (2 × 50 mL). The or-
ganic layer was separated and evaporated under reduced pressure to obtain
a syrupy liquid. The crude product was subjected to silica gel column chro-
matography (ethyl acetate:hexane, 2:8) to obtain a syrupy liquid (5 g, 90%
yield). The syrupy liquid was crystallized by addition of 1 mL of ethyl ac-
etate and allowing the mixture undisturbed overnight to obtain colorless crys-
tals. m.p. 67–69◦C; Rf 0.20 (ethyl acetate/hexane, 4:6); [α]2D5 = +10.79 (c 1.0,
CHCl3); IR (neat) νmaxcm−11637, 1456, 1371, 1252, 1114, 1070, 847, 738, 699,
584. 1H NMR (CDCl3/TMS, 400 MHz): δ 1.25, 1.29 (2 × s, 12H, 4 × CH3);
3.20–3.33 (m, 1H, morpholinyl); 3.40–3.70 (m, 6H, morpholinyl); 3.78–3.88 (m,
2H, CHaHbCH, morpholinyl); 3.97–4.11 (m, 3H, 2 × CH, CHaHbCH); 4.12–
4.20 (m, 1H, H-2); 4.31 (d, J = 2.8 Hz, 1H, CHCO); 4.42 (d, J = 11.5 Hz, 1H,
PhCHaHb); 4.59 (d, J = 11.5 Hz, 1H, PhCHaHb); 7.21–7.32 (m, 5H, Ar-H); 13C
NMR (CDCl3/TMS, 100 MHz): δ 25.2, 26.61, 26.67, 27.2 (4 × CH3); 43.2, 45.9 (2
× N-CH2); 66.9, 67.1 (2 × O-CH2, morpholinyl); 67.6 (CH2CH); 72.9 (CH2Ph);
76.94, 76.96 (C-4, C-5); 80.7 (C-3); 81.3 (CHCO); 109.7, 109.9 (2 ×CMe2); 127.8,
128.1, 128.5, 136.9 (Aromatic); 168.5 (CO); HRMS (TOF MS ES+) m/z [M+H]+
calcd. for C23H33NO7 436.2335, found 436.2340.

2-O-Benzylation in D-Gluconamide Derivative
271
The other 2-O-alkylated D-gluco-configured morpholine amides, 9b–i,
were prepared adapting the above procedure and using corresponding alkyl
halide.
1-morpholino-(2-O-para-methoxy-benzyl-3,4:5,6-di-O-isopropylidene)-D-
gluconamide (9b)
Rf 0.11 (ethyl acetate/hexane, 4:6); [α]2D5 = +15.79 (c 1.0, CHCl3); IR (neat)
νmaxcm−11627, 1514, 1248, 1067, 906, 724, 647, 513. 1H NMR (CDCl3/TMS, 400
MHz): δ 1.24, 1.27 (2 × s, 12H, 2 × C(CH3)2); 3.20–3.30 (m, 1H, morpholinyl);
3.43–3.67 (m, 5H, morpholinyl); 3.71 ( s, 3H, -OCH3 ), 3.78–3.87 (m, 2H, mor-
pholinyl); 3.94–4.10 (m, 4H, H-4, H-5, H-6, H-6ꢁ ); 4.12–4.17 (m, 1H, H-3);
4.26–4.28 (m, 1H, CHCO); 4.35 (d, Jgem = 11.2 Hz, 1H, ArCHaHb); 4.51 (d,
Jgem = 11.2 Hz, 1H, ArCHaHb); 6.79 (d, J = 8.4 Hz, 2H, aromatic); 7.15 (d, J =
8.4 Hz, 2H, aromatic ); 13C NMR (CDCl3/TMS, 100 MHz): δ 25.2, 26.5, 26.6,
27.1 (2 × C(CH3)2); 43.1, 45.9 (2 × N-CH2); 55.2 (OCH3); 66.9, 67.5 (2 × O-
CH2, morpholinyl); 68.0 (CH2CH); 72.5 (-OCH2Ar); 76.9, 80.5, 80.7, 80.9 (4 ×
CH); 109.6, 109.8 (2 ×CMe2); 113.8, 128.8, 129.6, 159.5 (aromatic); 168.5 (CO);
HRMS (TOF MS ES+) m/z [M+H]+ calcd. for C24H35NO8 466.2441, found
466.2445.
1-morpholino-{2-O-(3ꢁ,4ꢁ-dimethoxy-benzyl)-3,4:5,6-di-O-isopropylidene}-D-
gluconamide (9c)
Rf 0.11 (ethyl acetate/hexane, 4:6); [α]2D5 = +16.49 (c 1.0, CHCl3); IR
(neat) νmax cm−11632, 1515, 1455, 1240, 1066, 1026, 845, 512. 1H NMR
(CDCl3/TMS, 400 MHz): δ 1.24, 1.27 (2 × s, 12H, 2 × C(CH3)2); 3.20–3.40 (m,
1H, morpholinyl); 3.40–3.70 (m, 6H, morpholinyl); 3.86, 3.87 (2s, 3H, -OCH3),
3.95–4.01 (m, 2H); 4.02–4.09 (m, 2H); 4.13–4.17 (m, 1H, H-3); 4.28–4.29 (d, J =
2.4 Hz, 1H, CHCO); 4.37 (d, J = 11.2 Hz, 1H, ArCHaHb); 4.53 (d, J = 11.2 Hz,
1H, ArCHaHb); 6.82–6.86 (m, 3H, aromatic); 13C NMR (CDCl3/TMS, 100 MHz):
δ 25.2, 26.6, 26.7, 27.2 (2 × C(CH3)2); 43.1, 45.9 (2 × N-CH2); 55.90, 55.95 (2
× OCH3); 66.9, 67.5 (CH2-O-CH2); 68.0 (CH2CH); 72.9 (-OCH2Ar); 76.9, 80.5,
80.7, 80.9 (4 × CH); 109.6, 109.8 (2 ×CMe2); 120.6, 121.0, 148.9, 159.5 (aro-
matic); 168.5 (CO); HRMS (TOF MS ES+) m/z [M+H]+ calcd. for C25H37NO9
480.1225, found 480.1219.
1-morpholino-(2-O-prop-2ꢁ-enyl-3,4:5,6-di-O-isopropylidene)-D-gluconamide
(9d)
Rf 0.20 (ethyl acetate/hexane, 4:6); [α]2D5 = +10.19 (c 1.0, CHCl3); IR (neat)
1
νmaxcm−12986, 1635, 1457, 1437, 1371, 1252, 1214, 1114, 1067, 846, 750. H
NMR (CDCl3/TMS, 400 MHz): δ 1.26, 1.34, 1.38, 1.39 (4 × s, 12H, 2 × C(CH3)2);
3.60–3.92 (m, 8H, morpholino); 3.93–3.99 (m, 2H,); 4.03–4.10 (m, 1H); 4.11–
4.17 (m, 3H); 4.19–4.23 (dd, J1 = 6.8 Hz, J2 = 2.4 Hz,1H, OCHCH2); 4.31 (d,

B.N. Manjunath et al.
272
J = 2.8 Hz, 1H, CHCO); 5.20 (d, J = 10.8 Hz, 1H, olefin CHcHt ); 5.26–5.32 (d,
J1 = 17.2 Hz, J2 = 1.6 Hz, 1H, olefin CHcHt); 5.86–5.95 (m, 1H, olefin CH); 13
C
NMR (CDCl3/TMS, 100 MHz): δ 25.1, 26.59, 26.61, 27.2 (2 × C(CH3)2); 43.3,
45.9 (2 × N-CH2); 67.0, 67.2 (2 × O-CH2, morpholinyl); 67.7 (OCHCH2); 71.5
(-OCH2CHCH2); 76.8, 77.0, 80.8, 81.2 (4 × CH); 109.7, 109.8 (2 ×CMe2); 117.7
(olefin CH2) ; 133.4 (olefin CH); 168.7 (CO); HRMS (TOF MS ES+) m/z [M+H]+
calcd. for C19H31NO7 386.2179, found 386.2170.
1-morpholino-(2-O-prop-2ꢁ-ynyl-3,4:5,6-di-O-isopropylidene)-D-gluconamide
(9e)
Rf 0.20 (ethyl acetate/hexane, 4:6); [α]2D5 = +35.12 (c 1.0, CHCl3); IR (neat)
νmaxcm−12986, 1632, 1440, 1372, 1250, 1214, 1113, 1065, 1029, 845, 752, 666,
1
513. H NMR (CDCl3/TMS, 400 MHz): δ 1.27, 1.29, 1.32, 1.34 (4 × s, 12H, 2
× C(CH3)2); 2.42 (m, 1H, alkyne); 3.30–3.70 (m, 8H, morpholino); 3.84–3.90
(dd, J = 8.0, 4.8 Hz, 1H, OCHaHbCH); 3.91–4.18 (multiplets, 5H); 4.20–4.28
(dd, J1 = 16.0, 2.4 Hz, 1H, OCHaHbCH); 4.41 (d, J = 2.8 Hz, 1H, CHCO);
13C NMR (CDCl3/TMS, 100 MHz): δ 25.1, 26.6, 27.1 (2 × C(CH3)2); 43.2,
46.1 (2 × N-CH2); 57.9 (propargyl CH2), 66.9 (2 × O-CH2, morpholinyl); 67.6
{(CH3)2COCH2}; 75.6 (CH, alkyne); 76.9, 77.0, 79.7, 80.4 (4 × CH); 109.8,
110.2 (2 ×CMe2); 167.9(CO); HRMS (TOF MS ES+) m/z [M+H]+ calcd. for
C19H29NO7 384.2022, found 384.2032.
1-morpholino-{2-O-(2ꢁ-methoxyethoxy)methyl-3,4:5,6-di-O-isopropylidene}-D-
gluconamide (9f)
Rf 0.03 (ethyl acetate/hexane, 4: 6); [α]2D5 = +25.18 (c 1.0, CHCl3); IR (neat)
1
νmaxcm−12895, 1636, 1456, 1371, 1248, 1214, 1113, 1065, 1019, 846. H NMR
(CDCl3/TMS, 400 MHz): δ 1.27, 1.30, 1.33, 1.34 (4 × s, 12H, 2 × C(CH3)2);
3.29 (s, 3H, OCH3); 3.32–3.40 (m, 1H, morpholinyl); 3.45 (t, J = 4.4 Hz, 2H,
OCH2CH2OMe); 3.54–3.71 (m, 6H+2H, morpholinyl, CH2OCH3); 3.72–3.81
(m, 1H, morpholinyl); 3.82–3.87 (dd, Jgem = 7.6 Hz, J6a,5 = 5.6 Hz, 1H, Ha-
6); 3.92–3.97 (m, 1H, CH); 3.98–4.10 (m, 2H, 2 × CH); 4.12–4.16 (dd, Jgem
=
7.2 Hz, J6b,5 = 3.2 Hz, 1H, Hb-6); 4.50 (d, J2,3 = 2.8 Hz, 1H, CHCO); 4.72 (s,
2H, OCH2O); 13C NMR (CDCl3/TMS, 100 MHz): δ 25.1, 26.4, 26.7, 27.2 (2 ×
C(CH3)2); 42.9, 46.1 (2 × N-CH2); 58.9 (OCH3); 66.9, 67.3 (2 × O-CH2, mor-
pholinyl); 67.4 (CH2OCH3); 67.9 (C-6); 71.5 (-OCH2CH2OMe); 76.8, 76.9, 77.3,
80.3 (4 × CH); 95.6 (OCH2O); 109.6, 110.1 (2 ×CMe2); 168.2 (CO); HRMS (TOF
MS ES+) m/z [M+H]+ calcd. for C20H35NO9 434.2390, found 434.2392.
1-morpholino-(2-O-methyl-3, 4: 5, 6-di-O-isopropylidene)-D-gluconamide (9g)
Rf 0.28 (ethyl acetate/hexane, 3:7); [α]2D5 = +6.195 (c 1.0, CHCl3); IR
1
(neat) νmaxcm−11653, 1456, 1380, 1252, 1114, 1070, 847, 845, 512. H NMR
(CDCl3/TMS, 400 MHz): δ 1.34, 1.36, 1.37, 1.40 (4 × s, 12H, 2 × C(CH3)2); 3.42
(s, 3H, OCH3); 3.60–3.92 (m, 8H, morpholinyl); 3.94–3.98 (dd, 1H, Jgem = 8.0,

2-O-Benzylation in D-Gluconamide Derivative
273
J6,5 = 4.0 Hz, OCHaHbCH); 4.01–4.21 (m, 5H, H-2, H-3, H-4, H-5, Hb-6); 13C
NMR (CDCl3/TMS, 400 MHz): δ 25.2, 26.6, 26.67, 27.0, (2 × C(CH3)2); 43.2,
45.6 (2 × N-CH2); 66.0, 67.2 (2 × O-CH2, morpholinyl); 67.6 (OCH2CH); 80.6,
77.0, 76.6 (3 × CH); 83.5 (CHCO); 109.6, 109.7 (2 ×CMe2); 168.3 (CO); HRMS
(TOF MS ES+) m/z [M+H]+ calcd. for C17H30NO7, 360.2022, found 360.2019.
1-morpholino-(2-O-ethyl-3, 4: 5, 6-di-O-isopropylidene)-D-gluconamide (9h)
Rf 0.20 (ethyl acetate/hexane, 3:7); [α]2D5 = +15.189 (c 1.0, CHCl3); IR (neat)
νmax cm−11637, 1458, 1371, 1253, 1215, 1151, 1068, 846; 1H NMR (CDCl3/TMS,
400 MHz): δ 1.09–1.12 (t, 3H, J = 6.8 Hz, OCH2CH3); 1.21, 1.23, 1.24, 1.27,
(4 × s, 12H, 2 × C(CH3)2); 3.21–3.39 (m, 2H, OCH2CH3); 3.47–3.80 (m, 8H,
morpholinyl); 3.81–3.84 (dd, 1H, Jgem = 8.0 Hz, J6a,5 = 4.4 Hz, OCHaHbCH);
3.88–3.98 (m, 2H, 2 × CH); 3.99–4.02 (dd, Jgem = 8.0 Hz, J6b,5 = 5.2 Hz, 1H,
OCHaHb); 4.04–4.07 (dd, 1H,J3,4 = 7.2, J3,2 = 2.4 Hz, CHCHCO); 4.11–4.12 (d,
J = 2.4 Hz, 1H, CHCO); 13C NMR (CDCl3/TMS, 400 MHz): δ 14.9 (CH2CH3);
25.2, 26.6, 26.67, 27.0 (2 × C(CH3)2); 43.1, 45.7 (2 × N-CH2); 66.1 (OCH2CH3);
66.8, 67.1 (2 × O-CH2, morpholinyl); 67.5 (CH2CH); 76.7, 76.9, 80.8, (3 × CH);
81.7, (CHCO); 109.6, 109.7 (2 ×CMe2); 168.8 (CO); HRMS (TOF MS ES+) m/z
[M+Na]+ calcd. for C18H31NO7Na, 396.1998, found 396.1991.
1-morpholino-(2-O-1butyl-3, 4: 5, 6-di-O-isopropylidene)-D-gluconamide (9i)
Rf 0.2 (ethyl acetate/hexane, 3:7); [α]2D5 = +11.99 (c 1.0, CHCl3); IR (neat)
νmaxcm−12923, 1637, 1458, 1371, 1253, 1215, 1068, 846 H NMR (CDCl3/TMS,
400 MHz): δ 0.85 (t, 3H, J = 7.2, CH3CH2); 1.12–1.21 (m, 2H, butyl); 1.27,
1.28, 1.30, 1.32 (4s, 12H, 2 × C(CH3)2); 1.46–1.57 (m, 2H, butyl); 3.25–3.39
(m, 2H, OCH2CH2); 3.49–3.90 (m, 8H, morpholinyl); 3.81–4.04 (m, 3H, H-4,
H-5, Ha-6); 4.05–4.09 (m, 1H, Hb-6); 4.09–4.13 (dd, J3,4 = 6.4, J3,2 = 2.0 Hz,
1H,CHCHCO), 4.14–4.18 (d, J = 2.0 Hz, 1H, CHCO);13C NMR (CDCl3/TMS,
400 MHz): δ 13.8 (CH3CH2); 19.23 (CH2CH3); 25.1, 26.5, 26.6, 27.2 (2 ×
C(CH3)2); 31.7(CH2, butyl) 43.2, 45.8 (2 × NCH2); 67.1, 67.3 (2 × O-CH2,
morpholinyl); 67.6 (OCH2, butyl); 70.8 (OCH2CH); 76.8, 77.0, 81.0 (3 × CH);
82.2 (CHCO); 109.7, 109.8 (2 ×CMe2); 169.0 (CO) HRMS (TOF MS ES+) m/z
[M+Na]+ calcd. for C20H35NO7Na 424.2311, found 424.2311.
Representative Procedure for the Reduction of 2-O-alkylated
Morpholine Amides 9a–i to the Corresponding D-glucitols
3a–i
2-O-benzyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol (3a)
To a solution of the α-O-benzyl amide 9a (5 g, 11.5 mmol) in 10 mL of
ethanol, sodium borohydride (7.4 g, 185 mmol) was added and the reaction mix-
ture was stirred at 60◦C for 12 h. On completion of the reaction, as monitored

B.N. Manjunath et al.
274
by thin layer chromatography, the reaction mixture was allowed to cool and
ethanol was evaporated under reduced pressure. The residue obtained was
dissolved in 25 mL of water and the solution was neutralized using acetic
acid . The product was extracted using diethylether (2 × 30 mL) and the com-
bined ether extracts were evaporated under reduced pressure to obtain the
crude product. This was subjected to silica gel column chromatography (ethyl
acetate:hexane, 2.5:7.5) to give a colorless syrup (3.5 g, 86%). Rf 0.33 (ethyl
acetate/hexane, 4:6); [α]D25 = +26.38 (c 1.0, CHCl3); IR (neat) νmaxcm−13481,
1
1217, 1071, 772, 698, 669. H NMR (CDCl3/TMS, 400 MHz): δ 1.35, 1.39, 1.42
(3 × s, 12H, 4 × CH3); 3.60–4.20 (multiplets, 8H), 4.68 (d, J = 11.7 Hz, 1H,
PhCHaHb); 4.78 (d, J = 11.7 Hz, 1H, PhCHaHb); 7.25–7.39 (m, 5H, Ar-H); 13C
NMR (CDCl3/TMS, 100 MHz): δ 25.2, 26.4, 26.7, 27.2 (4 × CH3); 62.2 (CH2OH);
67.9 (C-O-CH2); 72.5 (C-O-CH2CH); 77.4, 77.9 (2 × CH); 78.1 (PhCH2); 81.9
(CHCH2OH); 109.77, 109.79 (2 ×CMe2); 127.7, 127.8, 127.9,128.5, 138.3 (aro-
matic); HRMS (TOF MS ES+) m/z [M+Na]+ calcd. for C19H28O6 375.1784,
found 375.1789.
2-O-alkylated morpholine amides 9b–i were reduced using the above pro-
cedure to the glucitols 3b–i.
2-O-para-methoxy-benzyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol (3b)
Rf 0.53 (ethyl acetate/hexanes, 4:6); [α]2D5 = +20.58 (c 1.0, CHCl3); IR
(neat) νmaxcm−13478, 1513, 1371, 1246, 1213, 1068, 1035, 845, 752, 667, 512.
1H NMR (CDCl3/TMS, 400 MHz): δ 1.27, 1.30, 1.31, 1.32 (4 × s, 12H, 2 ×
C(CH3)2); 3.51–3.55 (m, 1H, Ha-6 ); 3.65–3.70 (dd, Jgem = 12.0 Hz, J1,2 = 4.4
Hz, 1H, CHaHbOH); 3.72 (s, 3H, OCH3); 3.74–3.80 (dd, Jgem = 12.0 Hz, J1,2
=
4.4 Hz, 1H, CHaHbOH); 3.81–3.86 (dd, Jgem = 8.4 Hz, J6b,5 = 5.6 Hz, 1H, Hb-6);
3.90–4.01 (m, 2H, 2 × CH); 4.02–4.09 (m, 2H, 2 × CH); 4.53 (d, Jgem = 11.2
Hz, 1H, ArCHaHb); 4.60 (d, Jgem = 11.5 Hz, 1H, ArCHaHb); 6.78–6.81 (m, 2H,
aromatic ); 7.21–7.23 (m, 2H, aromatic); 13C NMR (CDCl3/TMS, 100 MHz): δ
25.4, 26.7, 26.9, 27.4 (2 × C(CH3)2); 55.5 (OCH3); 62.5 (CH2OH); 68.1 (C-6);
72.5 (OCH2Ar); 77.3, 77.5, 77.7, 81.9 (4 × CH); 109.6, 109.8 (2 ×CMe2); 113.8,
129.4, 129.6, 159.5 (aromatic); HRMS (TOF MS ES+) m/z [M+H]+ calcd. for
C20H29O7 383.2441, found 383.2445.
2-O-(3ꢁ,4ꢁ-dimethoxy-benzyl)-3, 4: 5, 6-di-O-isopropylidene-D-glucitol (3c)
Rf 0.46 (ethyl acetate/hexane, 4:6); [α]2D5 = +13.70 (c 1.0, CHCl3); IR (neat)
νmax cm−13512, 2934, 1515, 1371, 1260, 1238, 1213, 1068, 1027, 845, 751, 666,
1
512. H NMR (CDCl3/TMS, 400 MHz): δ 1.27, 1.31, 1.32, 1.34 (4 × s, 12H, 2
× C(CH3)2); 3.52–3.56 (m, 1H, Ha-6 ), 3.67–3.73 (dd, Jgem = 12.0 Hz, J1,2 = 4.4
Hz, 1H, CHaHbOH); 3.76–3.78 (m, 1H, CHaHbOH); 3.79, 3.81 (2 × s, 6H, 2 ×
OCH3), 3.82–3.87 (dd, Jgem = 8.4 Hz, J6b,5 = 5.6 Hz, 1H, Hb-6); 3.91–4.02 (m,
2H, 2 × CH); 4.05–4.11 (m, 2H, 2 × CH); 4.54 (d, Jgem = 11.6 Hz, 1H, ArCHaHb);

2-O-Benzylation in D-Gluconamide Derivative
275
4.62 (d, Jgem = 11.6 Hz, 1H, ArCHaHb); 6.75 (d, J = 8.0 Hz,1H, Ar-H); 6.80–6.83
(dd, J1 = 8.0 Hz, J2 = 1.6 Hz,1H, Ar-H); 6.88 (d, J = 1.6 Hz,1H, Ar-H); 13C NMR
(CDCl3/TMS, 100 MHz): δ 25.1, 26.4, 26.7, 27.2 (2 × C(CH3)2); 55.8, 55.9 (2 ×
OCH3); 62.3 (CH2OH); 67.8 (CH2CH); 72.5 (OCH2Ar); 77.2, 77.5, 77.9, 81.9
(4 × CH); 109.76, 109.78 (2 ×CMe2); 111.0, 111.3, 120.3, 130.9, 148.7, 149.1
(Aromatic); HRMS (TOF MS ES+) m/z [M+H]+ calcd. for C21H31O8 397.3351,
found 397.3346.
2-O-prop-2ꢁ-enyl-3,4:5,6-di-O-isopropylidene-D-glucitol (3d)
Rf 0.34 (ethyl acetate/hexane, 4:6); [α]2D5 = +4.99 (c 1.0, CHCl3); IR (neat)
νmaxcm−13448, 2986, 1371, 1248, 1212, 1152, 1067, 845, 512. 1H NMR
(CDCl3/TMS, 400 MHz): δ 1.28, 1.31, 1.35 (3 × s, 12H, 2 × C(CH3)2); 3.46–
3.52 (m, 1H); 3.68–3.80 (ddd, J1 = 12.0 Hz, J2 = 4.8 Hz, J3 = 0.8 Hz, 2H,
-OCH2CHCH2); 3.85–4.20 (multiplets, 7H); 5.10 (d, J = 11.2 Hz, 1H, olefin
CHcHt ); 5.19–5.27 (m, J1 = 16.6 Hz, 1H, olefin CHcHt); 5.81–5.94 (m, 1H,
olefin CH); 13C NMR (CDCl3/TMS, 100 MHz): δ 25.2, 26.4, 26.6, 27.1 (2 ×
C(CH3)2); 62.2 (CH2OH); 67.9 (C-6); 71.7 (-OCH2CHCH2); 77.3, 77.8, 81.8 (4
× CH); 109.7, 109.8 (2 ×CMe2); 117.0 (olefin CH2) ; 134.8 (olefin CH); HRMS
(TOF MS ES+) m/z [M+Na]+ calcd. for C15H26O6 325.1627, found 325.1622.
2-O-prop-2ꢁ-ynyl-3,4:5,6-di-O-isopropylidene-D-glucitol (3e)
Rf 0.40 (ethyl acetate/hexane, 4:6); [α]2D5 = +12.39 (c 1.0, CHCl3); IR (neat)
νmax cm−13432, 2986, 1440, 1372, 1250, 1214, 1113, 1065, 1029, 845, 752, 666,
1
513. H NMR (CDCl3/TMS, 400 MHz): δ 1.36, 1.38, 1.42, 1.44 (4 × s, 12H, 2
× C(CH3)2); 2.45 (m, 1H, alkyne); 3.72–3.77 (dd, J1 = 8.4 Hz, J2 = 4.4 Hz,1H,
CHCH2OH); 3.78–3.84 (dd, J = 12.0, 4.4 Hz, 1H, CHaHbOH); 3.86–3.92 (dd,
J = 12.0, 4.4 Hz, 1H, CHaHbOH); 3.93–3.98 (dd, J = 8.4, 5.6 Hz, 1H); 4.00
(d, J = 7.2 Hz, 1H); 4.03–4.10 (m, 1H); 4.11–4.15 (dd, J = 7.2, 4.4 Hz, 1H);
4.16–4.20 (dd, J1 = 8.4, 6.0 Hz, 1H); 4.32–4.47 (m, 1H); 13C NMR (CDCl3/TMS,
100 MHz): δ 25.2, 26.4, 26.7, 27.2 (2 × C(CH3)2); 57.8 (propargyl CH2), 62.2
(CH2OH); 67.9 {(CH3)2COCH2}; 74.8 (CH, alkyne); 77.3, 77.6, 77.8, 81.8 (4 ×
CH); 109.90, 109.92 (2 ×CMe2); HRMS (TOF MS ES+) m/z [M+H]+ calcd. for
C15H24O6 301.1122, found 301.1120.
2-O-(2ꢁ-methoxyethoxy)methyl-3,4:5,6-di-O-isopropylidene-D-glucitol (3f)
Rf 0.15 (ethyl acetate/hexane, 6:4); [α]2D5 = +25.18 (c 1.0, CHCl3); IR (neat)
νmaxcm−13467, 1456, 1380, 1249, 1212, 1126, 1065, 1035, 845. 1H NMR
(CDCl3/TMS, 400 MHz): δ 1.34, 1.37, 1.40, 1.41 (4 × s, 12H, 2 × C(CH3)2);
3.39 (s, 3H, OCH3); 3.56 (t, J = 4.4 Hz, 2H, OCH2CH2OCH3); 3.67–3.75 (m,
2H, H-4, Ha-6); 3.76–3.80 (m, 2H, CH2OH); 3.85–3.95 (m, 3H, CH2OCH3, H-
5); 4.01–4.08 (m, 2H, H-2, H-3); 4.13–4.19 (m, 1H, Hb-6); 4.78–4.81 (d, 1H,
J = 7.2 Hz, OCHaHbO); 4.90–4.94 (d, 1H, J = 7.2 Hz, OCHaHbO); 13C NMR

B.N. Manjunath et al.
276
(CDCl3/TMS, 100 MHz): δ 25.1, 26.4, 26.7, 27.1 (2 × C(CH3)2); 58.9 (OCH3);
63.5 (CH2OH); 67.5 (CH2OCH3); 67.9 (C-6); 71.6 (-OCH2CH2OMe); 77.3, 77.6,
80.9, 81.4 (4 × CH); 96.3 (OCH2O); 109.7, 109.8 (2 ×CMe2); HRMS (TOF MS
ES+) m/z [M+H]+ calcd. for C16H30O8 351.2019, found 351.2018.
2-O-methyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol (3g)
Rf 0.29 (ethyl acetate/hexane, 3:7); [α]2D5 = +14.5 (c 1.0, CHCl3); IR (neat)
1
νmax cm−13427, 1371, 1249, 1213, 1069, 846, 740, H NMR (CDCl3/TMS, 400
MHz): δ 1.28, 1.30, 1.34, 1.35 (4 × s, 12H, 2 × C(CH3)2); 2.60 (brs, OH); 3.30–
3.34 (m, 1H); 3.43 (s, OCH3); 3.67–3.83 (m, 2H, CH2OH); 3.88–3.92 (m, 2H);
3.96–4.03 (m, 2H); 4.07–4.13 (m,1H); 13C NMR (CDCl3/TMS, 100 MHz): δ 25.1,
26.4, 26.6, 27.0 (2 × C(CH3)2); 58.5 (OCH3); 61.5 (CH2OH); 67.9 (C-6); 77.2,
77.3, 80.6, 81.7 (4 × CH); 109.6, 109.7 (2 ×CMe2); HRMS (TOF MS ES+) m/z
[M+Na]+ calcd. for C13H24O6Na 299.1471, found 299.1473.
2-O-ethyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol (3h)
Rf 0.42 (ethyl acetate/hexane, 3:7); [α]2D5 = +22.18 (c 1.0, CHCl3); IR (neat)
1
νmax cm−13450, 1372, 1264, 1213, 1069, 846, 732, 512. H NMR (CDCl3/TMS,
400 MHz): δ 1.14–1.18 (t, 3H, J = 6.8Hz, CH3); 1.21, 1.23, 1.24,1.27 (4 ×
s, 12H, 2 × C(CH3)2); 3.42–3.44 (m, 1H, OCHaHbCH3);3.48–3.58 (m, 1H,
OCHaHbCH3); 3.65–3.72 (m, 1H, CHaHbOH); 3.73–3.78 (dd, 1H, J = 12.0, 4.8
Hz, CHaHbOH); 3.86–3.90 (m, 1H, CHaHbCH); 3.91–4.12 (m, 5H, H-2, H-3,
H-4, H-5, Hb-6); 13C NMR (CDCl3/TMS, 400 MHz): δ 15.37 (OCH2CH3); 25.1,
26.34, 26.5, 27.0 (2 × C(CH3)2); 62.2 (1 × CH2OH); 66.23 (OCH2CH3 ); 67.81
(OCH2CH); 76.7, 77.6, 78.06, 81.84 (4 × CH); 109.6, 109.7 (2 × C (CH3)3);
HRMS (TOF MS ES+) m/z [M+Na]+ calcd. for C14H26NO6Na, 313.1627, found
313.1630.
2-O-butyl-3, 4: 5, 6-di-O-isopropylidene-D-glucitol (3i)
Rf 0.20 (ethyl acetate/hexane, 3:7); [α]2D5 = +15.58 (c 1.0, CHCl3); IR (neat)
νmax cm−13499.9, 2992, 1370, 1210, 1067, 842, 735.1H NMR (CDCl3/TMS, 400
MHz): δ 0.88–0.93 (t, CH3CH2 ); 1.23 (m, 2H, CH2CH3); 1.32, 1.36,1.38, 1.39 (4s,
12H, 2 × C(CH3)2); 1.54–1.62 (m, 2H, OCH2CH2, butyl); 2.22–2.28 (brs, OH);
3.44–3.56 (m, 2H, OCH2, butyl ); 3.63–3.71 (m, 1H, H-2); 3.71–3.77 (dd, Jgem
12.0 Hz, J1,2 = 4.8 Hz, 1H, CHaHbOH); 3.81–3.87 (dd, Jgem = 12.0 Hz, J1,2
=
=
4.8 Hz, 1H, CHaHbOH); 3.91–3.96 (dd, Jgem = 8.4 Hz, J6a,5 = 5.2 Hz, 1H, Ha-6);
3.96–4.07 (m, 3H, H-3, H-4, H-5); 4.12–4.17 (dd, Jgem = 8.4 Hz, J6a,5 = 5.6 Hz,
1H, Hb-6); 13C NMR (CDCl3/TMS, 400 MHz): δ 13.9 (CH3CH2); 19.4 (CH2CH3);
25.2, 26.4, 26.6, 27.1 (2 × C(CH3)2); 32.1 (OCH2CH2, butyl); 62.3 (CH2OH);
67.9 (OCH2butyl); 70.7 (C-6); 77.2, 77.3, 78.02, 82.1 (4 × CH); 109.72,109.77
(2 ×CMe2); HRMS (TOF MS ES+) m/z [M+Na]+ calcd. for C16H30NO6Na,
341.1940, found 341.1941.

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277
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