Rapid assembly of the doubly-branched pentasaccharide domain of the immunoadjuvant jujuboside A: Via convergent B(C6F5)3-catalyzed glycosylation of sterically-hindered precursors

Article abstract of DOI:10.1039/c7cc01783a

A convergent synthesis of the complex, doubly-branched pentasaccharide domain of the natural-product immunoadjuvant jujuboside A is described. The key step is a sterically-hindered glycosylation reaction between a branched trisaccharide trichloroacetimida

Full text of DOI:10.1039/c7cc01783a

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Rapid assembly of the doubly-branched pentasaccharide domain
of the immunoadjuvant jujuboside A via convergent B(C6F5)3-
catalyzed glycosylation of sterically-hindered precursors
Received 00th January 20xx,
Accepted 00th January 20xx
Rashad R. Karimov,a* Derek S. Tana,b* and David Y. Gina,b†
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
convergent synthesis of the complex, doubly-branched >4-fold compared to no-adjuvant controls, approaching the
pentasaccharide domain of the natural-product immunoadjuvant increase observed with QS-21 (6.7-fold).7 In a subsequent
jujuboside A is described. The key step is a sterically-hindered study comparing the adjuvant and hemolytic activities of 47
glycosylation reaction between
trichloroacetimidate glycosyl donor and a disaccharide glycosyl much lower hemolytic activity than QS-21.8 This combination
acceptor. Conventional Lewis acids (TMSOTf, BF3 Et2O) were makes jujuboside A a promising adjuvant for further preclinical
a
branched trisaccharide saponins, jujuboside A showed higher adjuvant activity and
·
ineffective in this glycosylation, but B(C6F5)3 catalyzed the reaction investigation. Thus, as a part of our long-standing program on
9
successfully. Inherent complete diastereoselectivity for the saponin immunoadjuvants,6, we launched synthetic efforts
undesired α-anomer was overcome by rational optimization with toward the first chemical synthesis of jujuboside A, which
a nitrile solvent system (1:5 t-BuCN/CF3Ph) to provide flexible, would then enable systematic structure–activity relationship
effective access to the β-linked pentasaccharide.
(SAR) studies. Noting that the carbohydrate domain often
plays a key role in saponin immunoadjuvant activity, we first
sought to develop an efficient, flexible route to the complex,
doubly-branched pentasaccharide of jujuboside A. Herein, we
report the rapid, convergent synthesis of this pentasaccharide,
leveraging B(C6F5)3-catalyzed Schmidt glycosylation to join
hindered trisaccharide and disaccharide subunits.
Immunoadjuvants are critical components of modern
molecular vaccines that enhance or prolong the immune
response to antigens with which they are coadministered.1
Several saponin natural products exhibit immunoadjuvant
activity and the most frequently used are derived from the
Quillaja saponaria tree.2 Purified fraction QS-21, which is a
mixture of two isomeric saponins QS-21-Api and QS-21-Xyl,3 is
particularly active and widely used. It has been investigated
extensively in clinical vaccine development4 and is
a
component of the Mosquirix malaria vaccine.5 Although
Quillaja saponaria extracts have been shown to be effective in
various vaccine formulations, they have several drawbacks
including dose-limiting toxicity and chemical instability.4e
Thus, the development of new adjuvants with lower toxicity
and higher chemical stability is of great therapeutic interest.6
Jujuboside A (1, Figure 1) is a promising natural product
immunoadjuvant in this regard. Initial work by Yoshikawa
demonstrated that, in mice immunized with ovalbumin, coad-
ministration of jujuboside A increased antibody responses by
Figure 1. Structure and retrosynthesis of the saponin immunoadjuvant jujuboside A (1).
Saponins often contain an oligosaccharide that is branched
at a C2 position.10 Conventional synthetic approaches to such
branched oligosaccharides use a temporary protecting group
at C2 to facilitate the glycosylation reaction and control the
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stereochemistry of the newly formed glycosidic bond through activated with diphenylsulfoxide/triflic anhydride and reacted
neighboring group participation.11 This protecting group must with glycosyl acceptor
both prepared as previously
then be removed to allow installation of the C2 branching described,16 to deliver disaccharide
Scheme 1). Removal of
saccharide. Although this strategy provides effective control of the acetonide protecting group under acidic conditions gave
anomeric stereochemistry, it requires a linear synthesis. In diol Selective reprotection of the C4-hydroxyl of the
6,
7
(
8
.
contrast, direct coupling of glycan donors with a branching arabinopyranose through formation of a mixed orthoester
saccharide already installed at C2 would allow a more efficient followed by selective hydrolysis17 provided protected
and flexible convergent synthesis and facilitate SAR studies.
Our plan for assembly of the branched pentasaccharide for use in the key convergent glycosylation reaction below.
domain of jujuboside ( ) involved convergent coupling of a
Glc-Glc-Xyl trisaccharide glycosyl donor and Ara-Rha disac-
charide glycosyl acceptor . The -linked-diglucose fragment
corresponds to commercially available -gentiobiose. Thus,
disaccharide 3 with the arabinose C3-hydroxyl group available
1
2
3
β
β
the trisaccharide and disaccharide subunits could each be
assembled using a single glycosylation reaction. Although this
strategy is highly convergent, the key trisaccharide–
disaccharide coupling posed several challenges: 1) Both the
trisaccharide donor
3 and disaccharide acceptor 2 are highly-
substituted and sterically-hindered due to the C2 carbohydrate
appendages. 2) Due to this same C2 carbohydrate appendage
in glycosyl donor
boring group participation and, thus, obtaining the desired
-linkage could be challenging as coupling of hindered sub-
units is known to suffer from low yields and low -selectivity,
even with a C2 neighboring group.12 3) The glycosyl donor
has a C3-acetate, and electron-withdrawing substituents at
3, the reaction would not benefit from neigh-
β
β
3
this position are known to favor formation of
α
linkages.13
Scheme 2. Synthesis of glycosyl donor trisaccharide 2.
Assembly of Glc-Glc-Xyl trisaccharide subunit
2 began with
preparation of glycal 11
(
Scheme 2). Two procedures for
conversion of -gentiobiose octaacetate (
β
9
) to glycosylglucal
11 have been reported.18 In the first approach, AcOH/HBr is
used to prepare the corresponding glycosyl bromide, which
then undergoes elimination reaction to form the
Scheme 1. Synthesis of glycosyl acceptor disaccharide 3.
We noted that every glycosidic linkage in the jujuboside A
pentasaccharide has a 1,2-trans configuration and, therefore,
traditional neighboring group participation effects using ester
protecting groups could be leveraged in the synthesis of the
trisaccharide and disaccharide subunits.14 Thus, we focused on
acetyl and benzoyl protecting groups to enable global
deprotection at the completion of the synthesis. In addition to
their efficiency in controlling the desired 1,2-trans relative
stereochemistry, we envisioned that removal of these
protecting groups under basic conditions would be orthogonal
to the other functional groups present in the natural product.
corresponding glucal.18a
However, in our hands, this
procedure gave the disaccharide glycosyl bromide intermedi-
ate in low yield and purity. In the second approach, treatment
of β-gentiobiose octaacetate (9) with TiBr4 gave the desired
glycosyl bromide intermediate in high purity and yield.18b
However, subsequent elimination using Zn/Cu18b gave
inconsistent results. As an alternative, we found that
vanadium catalyst 10 combined with zinc as a stoichiometric
reducing agent effected elimination to glucosylglucal 11 in
good overall yield.19 Next, epoxidation of glycal 11 with
DMDO20 followed by epoxide opening with allyl alcohol,
furnished the disaccharide 12 with a free C2-hydroxyl group
for further extension. Coupling of disaccharide 12 with
Access to the Ara-Rha disaccharide
3 was achieved using the
dehydrative glycosylation method developed previously by our
group.15 The hemiacetal of protected rhamnose
5 was
2 | Chem. Commun., 2016, 00, 1-3
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trichloroacetimidate 13, prepared as previously described,21 coupling of trisaccharide
COMMUNICATION
2
and disaccharide
3
proceeded in
-linked
gave trisaccharide 14 as a single anomer. good yield, albeit providing the undesired
Detailed structural assignment using extensive NMR studies pentasaccharide -16 as the sole product (entry 3).
identified all three anomeric protons in trisaccharide 14, with The presence of an ester protecting group at the C3
H1–H2 coupling constants of 7.95, 7.69, and 4.00 Hz. The last position of hexose carbohydrate donors is known to favor
coupling constant was too small for typical -linked formation of -selectivity of our key
-glycosides.13 Thus, the
glycosydic bond. However, xylose can exist in an alternative glycosylation reaction is consistent with the presence of a C3-
1C4-conformation (via chair flip), which could explain this small acetate in trisaccharide donor
However, Mukaiyama has
α
α
a
β
α
α
2
.
coupling constant. This alternative conformation often results reported that solvent and counteranion also have dramatic
with ester protecting groups.22 Thus, to determine the effects on the stereochemical outcome of glycosylations.24 In
stereochemistry of newly formed glycosidic bond particular, combination of a t-BuCN/CF3Ph (1:5) solvent system
unambiguously, we removed all acetate and benzoate and HB(C6F5)4 catalyst favored formation of
β-glycosides.
protecting groups in trisaccharide 14 with NaOMe/MeOH. Unfortunately, use of HB(C6F5)4 in our key glycosylation
Analysis of the crude reaction product 15 using 1H- and reaction, resulted only in decomposition of trichloroacetimi-
2D-NMR confirmed that all glycosidic linkages were, indeed, in date
the -configuration (J = 8.01, 7.90, 7.77 Hz). Subsequently, Building upon our finding that reaction with B(C6F5)3 gave
deallylation of trisaccharide 14 using PdCl2,17 followed by tri- pentasaccharide
16 in good yield but undesired -selectivity
chloroacetimidate formation delivered trisaccharide donor (entry 3), we noted that nitrile-containing solvents are known
to favor 1,2-trans
-selectivity in glycosylation reactions.25 The
nitrile solvent is proposed to occupy the -face of the
oxocarbenium intermediate due to the anomeric effect,
resulting in addition of nucleophiles from -face. Accordingly,
2, in both CH2Cl2 and t-BuCN/CF3Ph (entries 4, 5).
β
α
-
α
2.
β
Table 1. Optimization of convergent glycosylation reaction to form pentasaccharide
α
16.a
β
after some optimization, we discovered that the combination
of B(C6F5)3 catalyst and t-BuCN/CF3Ph solvent system afforded
pentasaccharide 16 in 81% combined yield and 1.2:1
selectivity, overcoming the inherent complete stereoprefe-
rence for the undesired -anomer (entry 6). The desired
-anomer -16 could then be isolated in serviceable 42% yield.
Decreasing the temperature resulted in a slight erosion of
-selectivity and a significant decrease in yield (entry 7).
α/β
α
β
β
β
entry
reagent
TMSOTf
BF3∙OEt2
B(C6F5)3
HB(C6F5)4
HB(C6F5)4
B(C6F5)3
B(C6F5)3
solvent
CH2Cl2
temp (ºC) β : α Yieldb (%)
1
2
3
4
5
6
7
–20
–20
23
–
0c,d
7
CH2Cl2
CH2Cl2
52
0c
CH2Cl2
–78
–78
23
–
t-BuCN/CF3Phe
t-BuCN/CF3Phe
t-BuCN/CF3Phe
–
0c
1.2:1
1:1.2
81f
0
25
a Reactions were carried out with 0.01 mmol of trichloroimidate 2, 0.012 mmol of
disaccharide 3 and 0.1 equiv of the activator reagent. b Combined yield for α-16
c
d
and β-16. Decomposition of trichloroacetimidate 2 observed. This reaction
was also attempted at –78 °C, at 0 °C, and with the addition of 4 Å molecular
sieves, leading in all cases to decomposition of tricholoroimidate 2. e 1:5 ratio of
t-BuCN/CF3Ph. f Desired anomer β-16 isolated in 42% yield.
Scheme 3. Global deprotection of pentasaccharides β-16 and α-16 for stereochemical
assignment of newly-formed glycosidic bond.
With disaccharide
in hand, the stage was set for the key convergent coupling to
form doubly-branched pentasaccharide 16 Table 1). TMSOTf
is often used as a Lewis acid in Schmidt glycosylations,23 but
resulted only in decomposition of trichloroacetimidate (entry
1). Another commonly used Lewis acid, BF3∙OEt2,23 gave only
trace amounts of the undesired -anomer of pentasaccharide
3 and trisaccharide trichloroacetimidate 2
Stereochemical assignment of the newly formed glycosidic
bond was accomplished by a similar strategy to that used
above for trisaccharide 14. Thus, global deprotection of ester
(
protecting groups in
-17 and
-17, respectively (Scheme 3). 1H-NMR and HSQC
analysis of pentasaccharide -17 identified three anomeric
protons with large coupling constants (7.97, 7.81, 8.06 Hz),
corresponding to the three -linked glycosyl bonds. Two
additional anomeric protons with small coupling constants
(3.68, 1.69 Hz) were assigned to the -linked arabinose and
β-16 and α-16 gave pentasaccharides
2
β
α
β
α
16. In our group’s previous synthesis of the immunoadjuvant
QS-21, we found that B(C6F5)3 was superior to BF3∙OEt2 for
sterically-hindered glycosylations.9b Indeed, with this catalyst,
β
α
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Doucka, A. Flamen, B. Mordmuller and a. et, N. Engl. J. Med.,
2011, 365, 1863–1875.
rhamnose anomeric protons. In contrast, pentasaccharide
α-17 had only two anomeric protons with large coupling
constants (7.94, 7.75 Hz), corresponding to -linked terminal
5. The RTS,S Clinical Trials Partnership, PLoS Med., 2014, 11
e1001685.
,
β
glucose and xylose anomeric centers. Three other anomeric
6. A. Fernández-Tejada, D. S. Tan and D. Y. Gin, Acc. Chem. Res.,
2016, 49, 1741–1756.
protons with small coupling constants (3.69, 1.69, 0.96 Hz)
7. H. Matsuda, T. Murakami, A. Ikebata, J. Yamahara and M.
Yoshikawa, Chem. Pharm. Bull., 1999, 47, 1744–1748.
8. K. Oda, H. Matsuda, T. Murakami, S. Katayama, T. Ohgitani
and M. Yoshikawa, Biol. Chem., 2000, 381, 67–74.
9. (a) P. Wang, Y. J. Kim, M. Navarro-Villalobos, B. D. Rohde and
D. Y. Gin, J. Am. Chem. Soc., 2005, 127, 3256–3257; (b) Y. J.
Kim, P. F. Wang, M. Navarro-Villalobos, B. D. Rohde, J.
were observed, consistent with an
α
-linkage at the newly
formed glycosidic bond, in addition to the
and rhamnose residues.
α-linked arabinose
In conclusion, we have successfully synthesized the complex,
doubly-branched pentasaccharide domain of the immuno-
adjuvant jujuboside A (
route gave pentasaccharide
of 7 steps and 11% overall yield (73% per step average). The
trisaccharide ( ) and disaccharide ( ) subunits were construc-
1). Our highly convergent synthetic
Derryberry and D. Y. Gin, J. Am. Chem. Soc., 2006, 128
,
β
-16 in a longest linear sequence
11906–11915; (c) K. Deng, M. M. Adams, P. Damani, P. O.
Livingston, G. Ragupathi and D. Y. Gin, Angew. Chem. Int. Ed.,
2008, 47, 6395–6398; (d) K. Deng, M. M. Adams and D. Y.
Gin, J. Am. Chem. Soc., 2008, 130, 5860–5861; (e) M. M.
Adams, P. Damani, N. R. Perl, A. Won, F. Hong, P. O.
Livingston, G. Ragupathi and D. Y. Gin, J. Am. Chem. Soc.,
2010, 132, 1939–1945; (f) E. K. Chea, A. Fernández-Tejada, P.
Damani, M. M. Adams, J. R. Gardner, P. O. Livingston, G.
2
3
ted rapidly and late-stage convergent coupling using B(C6F5)3-
catalyzed glycosylation in an optimized t-BuCN/CF3Ph nitrile
solvent system overcame the steric hindrance and lack of
neighboring group participation in the substrate system,
providing effective access to the desired β-anomer. This sets
Ragupathi and D. Y. Gin, J. Am. Chem. Soc., 2012, 134
,
the stage for synthesis of the triterpenoid core and coupling to
this pentasaccharide to complete the natural product.
Although the stereoselectivity of the key glycosylation step is
moderate, the highly convergent nature of this synthetic
strategy is attractive for rapid generation of oligosaccharide
analogues of jujuboside A for SAR studies in the future.
We thank Prof. Samuel Danishefsky and Dr. William
Walkowicz for helpful discussions and Dr. G. Sukenick, Dr. H.
Liu, H. Fang, and Dr. S. Rusli (MSKCC) for expert mass spectral
analyses. Financial support from the NIH (R01 GM058833 to
D.S.T. and D.Y.G. and P30 CA008748 to C. B. Thompson) is
gratefully acknowledged.
13448–13457; (g) A. Fernández-Tejada, E. K. Chea, C. George,
N. Pillarsetty, J. R. Gardner, P. O. Livingston, G. Ragupathi, J.
S. Lewis, D. S. Tan and D. Y. Gin, Nat. Chem., 2014, 6, 635–
643.
10. B. Dinda, S. Debnath, B. C. Mohanta and Y. Harigaya, Chem.
Biodivers., 2010, , 2327-2580.
11. Y. Yang, S. Laval and B. Yu, Adv. Carbohyd. Chem. Biochem.,
7
2014, 71, 137-226.
12. A. M. Szpilman and E. M. Carreira, Org. Lett., 2009, 11, 1305–
1307.
13. (a) D. Crich and Q. J. Yao, J. Am. Chem. Soc., 2004, 126
,
8232–8236; (b) N. Ustyuzhanina, B. Komarova, N. Zlotina, V.
Krylov, A. Gerbst, Y. Tsvetkov and N. Nifantiev, Synlett, 2006,
921-923; (c) D. Crich and S. Picard, J. Org. Chem., 2009, 74,
9576–9579; (d) D. Crich and I. Sharma, J. Org. Chem., 2010,
75, 8383–8391.
14. T. Nukada, A. Berces, M. Z. Zgierski and D. M. Whitfield, J.
Am. Chem. Soc., 1998, 120, 13291–13295.
15. (a) B. A. Garcia, J. L. Poole and D. Y. Gin, J. Am. Chem. Soc.,
1997, 119, 7597–7598; (b) B. A. Garcia and D. Y. Gin, J. Am.
Chem. Soc., 2000, 122, 4269–4279.
16. (a) P. Y. Jeong, M. Jung, Y. H. Yim, H. Kim, M. Park, E. M.
Hong, W. Lee, Y. H. Kim, K. Kim and Y. K. Paik, Nature, 2005,
433, 541-545; (b) P. Finch, G. M. Iskander and A. H.
Siriwardena, Carbohydr. Res., 1991, 210, 319-325.
17. S. C. Bang, H. H. Seo, H. Y. Yun and S. H. Jung, Chem. Pharm.
Bull., 2007, 55, 1734-1739.
Notes and references
1. M. J. McCluskie and R. D. Weeratna, Curr. Drug Targets
Infect. Disord., 2001, 1, 263–271.
2. C. R. Kensil, U. Patel, M. Lennick and D. Marciani, J.
Immunol., 1991, 146, 431–437.
3. S. Soltysik, D. A. Bedore and C. R. Kensil, Ann. N. Y. Acad. Sci.,
1993, 690, 392–395.
4. (a) J. S. Kennedy, M. Co, S. Green, K. Longtine, J. Longtine, M.
A. O'Neill, J. P. Adams, A. L. Rothman, Q. Yu, R. Johnson-Leva,
R. Pal, S. Wang, S. Lu and P. Markham, Vaccine, 2008, 26
,
18. (a) A. G. Tolstikov, O. F. Prokopenko, R. K. Yamilov and G. A.
Tolstikov, Mendeleev Cummun., 1991, 1, 64–65; (b) A. H.
Franz, Y. Q. Wei, V. V. Samoshin and P. H. Gross, J. Org.
Chem., 2002, 67, 7662–7669.
19. R. V. Stick, K. A. Stubbs, D. M. G. Tilbrook and A. G. Watts,
Aust. J. Chem., 2002, 55, 83–85.
4420–4424; (b) P. Vandepapeliere, Y. Horsmans, P. Moris, M.
Van Mechelen, M. Janssens, M. Koutsoukos, P. Van Belle, F.
Clement, E. Hanon, M. Wettendorff, N. Garcon and G.
Leroux-Roels, Vaccine, 2008, 26, 1375–1386; (c) K. Von
Eschen, R. Morrison, M. Braun, O. Ofori-Anyinam, E. De Kock,
P. Pavithran, M. Koutsoukos, P. Moris, D. Cain, M. C. Dubois,
20. R. L. Halcomb and S. J. Danishefsky, J. Am. Chem. Soc., 1989,
111, 6661–6666.
21. L. Q. Chen and F. Z. Kong, Carbohydr. Res., 2002, 337, 2335–
2341.
J. Cohen and W. R. Ballou, Hum. Vaccin., 2009, 5, 475–482;
(d) B. Vellas, R. Black, L. J. Thal, N. C. Fox, M. Daniels, G.
McLennan, C. Tompkins, C. Leibman, M. Pomfret, M.
Grundman and A. N. S. Team, Curr. Alzheimer. Res., 2009,
6
,
22. F. W. Lichtenthaler, T. Schneideradams and S. Immel, J. Org.
Chem., 1994, 59, 6735-6738.
23. R. R. Schmidt and K. H. Jung, in Preparative Carbohydrate
Chemistry, ed. S. Hanessian, Marcel Dekker, New York, 1997,
p. 283.
144–151; (e) G. Ragupathi, J. R. Gardner, P. O. Livingston and
D. Y. Gin, Expert Rev. Vaccines, 2011, 10, 463–470; (f) E. Van
Braeckel, P. Bourguignon, M. Koutsoukos, F. Clement, M.
Janssens, I. Carletti, A. Collard, M. A. Demoitie, G. Voss, G.
Leroux-Roels and L. McNally, Clin. Infect. Dis., 2011, 52, 522–
531; (g) S. T. Agnandji, B. Lell, S. S. Soulanoudjingar, J. F.
Fernandes, B. P. Abossolo, C. Conzelmann, B. G. Methogo, Y.
24. H. Jona, H. Mandai and T. Mukaiyama, Chem. Lett., 2001,
426–427.
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25. S. K. Mulani, W. C. Hung, A. B. Ingle, K. S. Shiau and K. K. T.
Mong, Org. Biomol. Chem., 2014, 12, 1184–1197.
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