Syntheses of the D-aldopentoses from non-carbohydrate sources

Article abstract of DOI:10.1055/s-1999-3179

The cis-1,2-dihydrocatechols 5-7, which are obtained in high yield and ca. 99.8% ee by microbial oxidation of the corresponding aromatic compound, have been converted, via reaction sequences involving three distinct types of one-carbon deletion processes, into the four D-aldopentoses.

Full text of DOI:10.1055/s-1999-3179

LETTER
885
Syntheses of the D-Aldopentoses from Non-carbohydrate Sources
Martin G. Banwell,*a Chris De Savi,a David C. R. Hockless,a Susanne Pallicha and Keith G. Watsonb
a Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia
Fax +61-2-62495995; E-mail: mgb@rsc.anu.edu.au
b Biota Chemistry Laboratory, Chemistry Department, Monash University, Clayton, Victoria 3168, Australia
Fax +61-3-99055506; E-mail: Keith.Watson@sci.monash.edu.au
Received 1 February 1999
Dedicated to Professor Albert Eschenmoser in recognition of his seminal contributions to so many aspects of chemistry and chemical
biology
which deletes two carbons, followed by Wittig olefination
Abstract: The cis-1,2-dihydrocatechols 5-7, which are obtained in
chemistry to reinstate one carbon. It is against such a
background that we now wish to report carbon-atom effi-
high yield and ca. 99.8% ee by microbial oxidation of the corre-
sponding aromatic compound, have been converted, via reaction se-
cient syntheses of the title compounds from the cis-1,2-di-
hydrocatechols 5-7 which are themselves readily obtained
in large quantity and high enantiomeric excess by micro-
bial oxidation of the corresponding halobenzene.10,11
quences involving three distinct types of one-carbon deletion
processes, into the four D-aldopentoses.
Key words: D-arabinose, 1,2-diol cleavage, cis-1,2-dihydro-
catechol, D-lyxono-d-lactone, D-lyxose, ozonolytic cleavage, D-
ribose, radical decarboxylation, D-xylose
The D-aldopentoses 1-4 and their derivatives are of con-
siderable interest as starting materials for chemical syn-
thesis,1 as building blocks in the construction of
carbohydrate-based drugs2 and as probes of various bio-
chemical processes.3 Consequently, new methods for the
preparation of differentially protected and/or isotopically
labelled forms of these compounds should prove valuable.
The capacity to prepare such five-carbon sugars, especial-
ly 17O-, 13C- and/or 2H-labelled variants,4 could be greatly
facilitated by using appropriate non-carbohydrate based
starting materials.4b,5 However, in contrast to the consid-
erable effort that has been devoted to the synthesis of var-
ious pentitols6 and the aldohexoses,7 much of which
exploits asymmetric epoxidation chemistry, examples of
the preparation of the aldopentoses from non-carbohy-
drate sources remain rather limited.3c,8 In an important
contribution to the general area, Hudlicky et al.9 have
demonstrated that the enantiopure six-carbon cis-1,2-di-
hydrocatechol 5 can be converted into L-ribono-g-lactone
acetonide. The key steps involved initial ozonolysis,
Scheme 1 Reagents and conditions: (i) see ref. 12; (ii) see ref. 12; (iii)
TBDMSCl (2.95 mole equiv.), Hünig's base (3.8 mole equiv.), DMF,
18 °C, 8 h; (iv) ozone (excess), MeOH, -78 °C, 10 min., then
NaBH3CN (ca. 6.0 mole equiv.), HCl (2 M in MeOH), 0 to 18 °C, ca.
2.5 h; (v) DIBALH (2.5 mole equiv.), CH2Cl2, -78 °C, 2 h then quench
with MeOH; (vi) 4:1 v/v TFA/H2O, 18 °C, 18 h.
A concise synthesis of D-lyxose (2) from compound 5 is
shown in Scheme 1 and involves initial conversion of the
starting material into the corresponding acetonide 8.12
This derivative undergoes a b-face selective reaction with
singlet-oxygen and the resulting endoperoxide is immedi-
ately cleaved with thiourea to give the previously
reported12 g-hydroxyenone 9 (ca. 38% from 5). In the key
step of the reaction sequence, the readily derived tert-bu-
tyldimethylsilyl (TBDMS)-ether, 10 {80%, m.p. < 50 °C
(lit.12 m.p. = 50-54 °C), [a]D = -74 (c 5.5)13}, of compound
9 was subjected to ozonolytic cleavage followed by a re-
ductive "work-up" using sodium cyanoborohydride at pH
3.14 In this way the lactone 11 {82%, m.p. = 61-62.5 °C,
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886
M. G. Banwell et al.
LETTER
[a]D = -35 (c 1.6)} was obtained.15 This last compound amongst the complex mixture of reaction products. That
was readily converted into the target aldopentose by di- analogue of compound 17 in which the TBDMS-group
isobutylaluminium hydride (DIBALH)-mediated reduc- has been replaced by an acetyl moiety also failed to under-
tion of the lactone moiety to the corresponding lactol 12 go the desired type ozonolytic-cleavage reaction. Conse-
{95%, m.p. = 91-91.5 °C, [a]D = -15 (c 1.0 - rotation de- quently, an alternate route from the cis-1,2-
termined after 24 h)} which when treated with aqueous dihydrocatechols 5-7 to D-ribose had to be devised (see
trifluoroacetic acid (TFA) afforded D-lyxose (2) {82%, Scheme 3).
m.p. = 115 °C (decomp.), [a]D = -17 (c 1.0 in H2O - rota-
tion determined after 25 h)}. This material was identical,
in all respects, with an authentic sample obtained from Al-
drich™.
Efforts to adapt the above-mentioned chemistry so as to
access D-ribose are shown in Scheme 2 and start with the
g-hydroxyenone 9 which was protected as the triethylsilyl
(TES)-ether 13 {97%, [a]D = -38 (c 1.9)} under standard
conditions. L-Selectride-mediated reduction of this latter
compound provided allylic alcohol 14 {[a]D = -100
(c 1.8)} as the only isolable product of reaction albeit in
30% yield. Reaction of compound 14 with tert-butyldim-
ethylsilyl triflate (TBDMSOTf) in pyridine then gave the
TBDMS-ether 15 {96%, [a]D = -92 (c 1.6)} which upon
treatment with aqueous acetic acid in THF resulted in re-
moval of the TES-group to afford alcohol 16 {100%, [a]D
= -97 (c 1.2)}.
Scheme 3 Reagents and conditions: (i) TBDPSCl (1.1 mole equiv.),
imidazole (3.0 mole equiv.), CH2Cl2, 18 °C, 7 h; (ii) OsO4 (cat.),
NMO (1.3 mole equiv.), 3:1 v/v Me2CO/H2O, 4 °C, 30 h; (iii)
Me2C(OMe)2, p-TsOH (cat.), 18 °C, 3 h; (iv) ozone (excess), MeOH,
-78 °C, 0.5 h then NaBH3CN (ca. 6.0 mole equiv.), HCl (2 M in Me-
OH), 0 to 18 °C, ca. 2.5 h; (v) LiBH4 (5 mole equiv.), MeOH (5 mole
equiv.), Et2O, reflux, 6 h; (vi) NaIO4 (2 mole equiv.), 3:1 v/v MeOH/
H2O, 18 °C, 3 h; (vii) 10% v/v aq. HCl, 18 °C, 18 h.
A reaction sequence for the conversion of monochiral diol
7 into D-arabinose is shown in Scheme 3 and serves to
highlight an alternate one-carbon deletion process that al-
lows for the conversion of cis-1,2-dihydrocatechols into
aldopentoses. Thus, reaction of compound 7 with tert-bu-
tyldiphenylsilyl (TBDPS)-chloride under carefully con-
trolled conditions resulted in selective protection of the
less-hindered hydroxyl group within the substrate and the
formation of the rather unstable ether 19 (97%). Diastere-
Scheme 2 Reagents and conditions: (i) TESCl (3 mole equiv.), Hü-
nig's base (4.0 mole equiv.), DMF, 18 °C, 16 h; (ii) L-Selectride (1.1
mole equiv.), THF, -78 °C, 5 min; (iii) TBDMSOTf (3.0 mole equiv.),
pyridine (5.0 mole equiv.), CH2Cl2, 0-5 °C, 2 h; (iv) 11:5:3 v/v/v
AcOH/THF/H2O, 18 °C, 4 h; (v) TPAP (0.05 mole equiv.), NMO (3
mole equiv.), 4 Å molecular sieves, CH2Cl2, 18 °C, 16 h; (vi) ozone
(excess), MeOH, -78 °C, 10 min., then NaBH3CN (ca. 6.0 mole
ofacially-selective cis-1,2-dihydroxylation of the latter
equiv.), HCl (2 M in MeOH), 0 to 18 °C, ca. 1.5 h. NMO = N-methyl-
compound could be effected under standard conditions17
morpholine N-oxide; TPAP = tetrapropylammonium perruthenate.
and the resulting diol 20 was immediately converted, by
conventional means, into the corresponding acetonide 21
{ca. 80% from 19, m.p. < 25 °C, [a]D = +19 (c 1.4)}. Re-
Oxidation of the last compound with the Ley-Griffith
action of compound 21 with ozone in methanol followed
reagent16 produced enone 17 {80%, [a]D = -102 (c 1.0)}
by a reductive "work-up" using sodium cyanoborohydride
at low pH provided the methyl ester 22 {77%, m.p. = 145-
but when this material was subjected to the same condi-
tions as used to effect the conversion 10 Æ 11 the desired
147 and 156-158 °C, [a]D =+41 (c 1.3, determined after 64
D-ribono-d-lactone derivative 18 could not be detected
h)}. The structure of compound 22 was confirmed by sin-
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LETTER
Syntheses of the D-Aldopentoses from Non-carbohydrate Sources
887
gle crystal X-ray analysis18 of its a-anomer which crystal- molybdenum(VI) oxide bis-2,4-pentanedionate has been
lised from mixtures of 1,2-dimethoxyethane and hexane.
shown19 to provide the L-enantiomer of the latter in ca.
28% yield.
Reduction of both the ester and lactol moieties within
compound 22 was effected with lithium borohydride and Developing a synthesis of D-xylose (4) from the cis-1,2-
the resulting triol 23 {71%, [a]D = +28 (c 3.9)} was sub- dihydrocatechols proved the most demanding aspect of
jected to oxidative cleavage using sodium metaperiodate the present work and, ultimately, a radical-decarboxyla-
thereby producing a protected form, 24 {80%, [a]D = -24 tion process was used to effect the necessary one-carbon
(c 3.5 - determined after 30 h)}, of target 1. Treatment of deletion step. The initial stages of the synthesis (Scheme
lactol 24 with 10% aqueous HCl then provided D-arabi- 4) involved epoxidation of the acetonide derivative of bro-
nose itself {68%, m.p. = 158 °C (decomp.), [a]D = -104 (c modiol 6 so as to generate the previously reported20 ox-
1.0, H2O - determined after 48 h)} which was identical, in irane 25 (>80% from 6). Ring-opening of the epoxide
all respects, with an authentic sample obtained from Ald- moiety within the latter compound could be achieved us-
rich™.
ing water as the nucleophile and HCl as catalyst so as to
produce the previously reported21 trans-diol 26 {92%,
m.p. = 147 °C, [a]D = -4 (c 1.0)}. The regioselectivity ex-
hibited in this conversion is consistent with related cleav-
ages of similar epoxides22 where-in the newly introduced
hydroxyl group derives from attack of the nucleophile at
the allylic position within substrate 25. Compound 26 was
converted into the corresponding bis-TBDMS-ether
27{89%, m.p. = 101.5-102.5 °C, [a]D = +43 (c 1.1)} and
this latter compound subjected to ozonolysis in methanol
then "work-up" with sodium borohydride. In this fashion
the hydroxy-ester 28 {85%, [a]D = -10 (c 10.0)} was ob-
tained and could be converted into the corresponding 2-
methoxyethoxymethyl (MEM)-ether 29 {99%, [a]D = -4
(c 1.9)} under standard conditions. Using the carefully
controlled conditions reported by Crich23 the ester moiety
within this latter compound could be converted into the
corresponding acid 30 {100%, [a]D = -9 (c 1.7)} without
any complications arising from cleavage of the silyl ether
units.
The ester derived from condensation of acid 30 with 2-
mercaptopyridine N-oxide was then photolysed in the
presence of tert-dodecanethiol23 to afford the radical de-
carboxylation product 31 {45% from 30, [a]D = -31 (c
0.7)} which was desilylated under standard conditions
and the resulting vic-diol 32 immediately reprotected as
the corresponding acetonide 33 {68% from 31, [a]D =-9 (c
0.2)}. Removal of the MEM-group within this last com-
pound was achieved by sequential treatment with n-BuLi
then Hg(OAc)224 and the resulting xylitol derivative 34
{45%, [a]D = -12 (c 2.5, MeOH)}25 oxidised to the alde-
hyde 35 {92%}26 using the Dess-Martin periodinane.27 Fi-
nally, deprotection of the last compound using aqueous
hydrochloric acid afforded D-xylose (4) itself (30%) the
tetra-O-acetyl-b-D-pyranose derivative {m.p. = 127-128
°C, [a]D = -23 (c 0.5)} of which proved identical with an
authentic sample {m.p. = 126-127 °C, [a]D =-25 (c 2.0)}28
derived from commercially available D-xylose.
Scheme 4 Reagents and conditions: (i) ref 20; (ii) ref 20; (iii) 1% v/v
HCl in THF, 2:1 v/v THF/H2O, 18 °C, 16 h; (iv) TBDMSOTf (3.6
mmol), 2,6-lutidine (6.0 mole equiv.), CH2Cl2, 18 °C, 18 h; (v) ozone
(excess), 1:1 v/v MeOH/CH2Cl2 , -78 °C, 0.5 h then NaBH4 (4.0 mole
equiv.), 0-18 °C, 3.5 h; (vi) MEM-Cl (5.5 mole equiv.), Hünig's base
(3.0 mole equiv.), CH2Cl2, 18 °C, 18 h; (vii) KOH (3.0 mole equiv.),
THF, MeOH, H2O, 18 °C, 18 h then 10% v/v aq. HCl; (viii) 2-mer-
captopyridine N-oxide (1.15 mole equiv.), DCC (1.0 mole equiv.),
Et2O, 18 °C, 2 h then tert-dodecanethiol (1.86 mole equiv.), irradiati-
on (400 W high pressure Hg lamp), 18 °C, 2h; (ix) TBAF (4.0 mole
equiv.), THF, 18 °C, 18 h; (x) Me2C(OMe)2, p-TsOH (cat.), 18 °C, 3
h; (xi) n-BuLi (4.0 mole equiv.), THF, 18 °C, 10 h then Hg(OAc)2 (2.5
mole equiv.), 1:1 v/v THF/H2O, 18 °C, 5 h; (xii) Dess-Martin periodi-
nane (2.5 mole equiv.), CH2Cl2, 18 °C, 1.5 h; (xiii) 6% v/v aq. HCl,
18 °C, 18 h. TBAF = tetra-n-butylammonium fluoride.
The work described here-in, especially when considered
alongside previous reports from these29 and other labora-
tories,5,11 should serve to emphasise the considerable util-
ity and potential of cis-1,2-dihydrocatechols as starting
materials for the synthesis of monosaccharides and vari-
ous derivatives there-of.
The acquisition of D-arabinose (1) by the method just de-
scribed also constitutes a formal total synthesis of D-ri-
bose (3) from non-carbohydrate sources since treatment
of the L-enantiomer of the former compound with
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888
M. G. Banwell et al.
LETTER
(11) For a concise review on the applications of cis-1,2-dihydro-
catechols in synthesis see Hudlicky, T.; Thorpe, A. J. Chem.
Commun., 1996, 1993.
(12) Hudlicky, T., Rulin, F., Tsunoda, T., Luna, H., Andersen, C.;
Price, J. D., Isr. J. Chem., 1991, 31, 229.
Acknowledgment
We thank Drs Larry Kwart and Gregg Whited (Genencor Interna-
tional Inc.) for providing samples of compounds 5-7, the Institute of
Advanced Studies for generous financial support and the Australian
Research Council for provision of an APA(I) PhD Scholarship (to
CDS).
(13) Unless otherwise specified, optical rotations were determined
in CHCl3 at 20 °C.
(14) This type of ozonolytic cleavage of cyclic enones has been de-
scribed previously (Chavdarian, C. G.; Heathcock, C. H. J.
Org. Chem., 1975, 40, 2970). For related cleavages that do not
involve a reductive "work-up" see Cella, J. A., Synth. Com-
mun., 1983, 13, 93.
(15) The L-enantiomer of compound 11 has been reported
previously: Saburi, M.; Ishii, Y.; Kaji, N.; Aoi, T.; Sasaki, I.;
Yoshikawa, S.; Uchida, Y. Chem. Lett., 1989, 563.
(16) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P.
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(17) Ray, R.; Matteson, D. S. Tetrahedron Lett., 1980, 21, 449.
(18) Crystal structure data have been deposited with the Cam-
bridge Crystallographic Data Centre (CCDC) and can be
obtained by directing enquiries to the following address: The
Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ,
United Kingdom.
References and Notes
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Article Identifier:
1437-2096,E;1999,0,S1,0885,0888,ftx,en;W04799ST.pdf
(10) See Zylstra, G. J.; Gibson, D. T. J. Biol. Chem., 1989, 264,
14940 and references cited there-in.
Synlett 1999, S1, 885–888 ISSN 0936-5214 © Thieme Stuttgart · New York