Conceptualization and Synthesis of the First Inosito-Inositol (Decahydroxydecalin, DHD): In silico Binding to β-Amyloid Protein

Article abstract of DOI:10.1002/chem.202003367

Previously unknown entities in the form of 1,2,3,4,5,6,7,8,9,10-decahydroxydecalins (DHDs) have been conceptualized and the first member of this class, an inosito-inositol, has been synthesized from aromatic hydrocarbon naphthalene following a flexible strategy that is amenable to diversity creation. The DHD accessed here has been subjected to preliminary in silico evaluation with Aβ and may hold some promise in Alzheimer's disease therapeutics.

Full text of DOI:10.1002/chem.202003367

Accepted Article
Accepted Article
Title: Conceptualization and synthesis of first inosito-inositol
(decahydroxydecalin, DHD): In silico binding to β-amyloid protein
Authors: Bilal Bhat, Showkat Rashid, and Goverdhan Mehta
This manuscript has been accepted after peer review and appears as an
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to this Accepted Article as a result of editing. Readers should obtain
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To be cited as: Chem. Eur. J. 10.1002/chem.202003367
Link to VoR: https://doi.org/10.1002/chem.202003367
01/2020

10.1002/chem.202003367
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Conceptualization
and
synthesis
of
first
inosito-inositol
(decahydroxydecalin, DHD): In silico binding to -amyloid protein
Showkat Rashid, [a,b] Bilal A. Bhat* [a,b] and Goverdhan Mehta*[c]
[a]
Dr. Bilal A. Bhat, Dr. Showkat Rashid
CSIR-Indian Institute of Integrative Medicine
Jammu & Kashmir, India
E-mail: bilal@iiim.res.in (BAB)
[b]
[c]
Academy of Scientific and Innovative Research, India
Prof. Goverdhan Mehta
School of Chemistry, University of Hyderabad,
Hyderabad 500046, India
E-mail:gmsc@uohyd.ernet.in (GM)
Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate))
efforts have been mounted to create structural and functional
diversity around their poly-oxygenated architecture to map and
amplify their bioactivity potential. These forays have broadly
ranged from diversified regioselective derivatization of readily
available inositols,[7] synthesis and approaches to their
numerous ring size variants like 4-,5-,8- and 9-membered
cyclitols (4-7)[8] and crafting of bi- and tricyclic analogues
(polycyclitols, 8-12) that may either augment or unravel new
biological activities.[9] Some of these new constructs have
emanated from our group and from others and representative
ones are displayed in Figure 2.
Abstract: Previously unknown entities in the form of
1,2,3,4,5,6,7,8,9,10-decahydroxydecalins (DHDs) have been
conceptualized and the first member of this class, an inosito-inositol,
has been synthesised from aromatic hydrocarbon naphthalene
following a flexible strategy that is amenable to diversity creation.
The DHD accessed here has been subjected to preliminary in-silico
evaluation with Aand may hold some promise in Alzheimer’s
therapeutics.
Inositols represent an important class of naturally occurring
bioactive, oxygenated cyclohexanoids, characterized by specific
disposition of hydroxyl groups on each of their six carbon
centres in variegated stereochemical patterns (Figure 1). Being
formally carbasugar siblings, harboring dense oxygen
functionality, inositols have been found to play a key role in
numerous biological functions in plant and animal tissues.
Notably they are involved in inter- and intracellular
communication by mediating cell signal transductions, exhibit
insulin mimetic attributes by acting as secondary messengers in
the insulin intracellular pathway stimulation, phosphate storage
& transfer and anchoring of certain important proteins to cell
membrane, etc.[1-3] Recently, inositols have been proposed for
the safe management of polycystic ovary syndrome (PCOS) in
women and treatment of gestational diabetes mellitus (GDM).[3f]
myo-inositol (1) and inositol phosphates (InsPs) among other
siblings have been implicated and investigated for inhibiting
various cancer types and for providing chemo-protection.[4]
Significantly, the role of myo- (1), epi- (2) and scyllo- (3)
inositols in dementia, caused by the Alzheimer’s disease (AD)
has created much excitement and 3 in particular has been
shown to coat the surface of A protofibrils and disrupt their
stacking into fibrillar aggregates. In addition to the efficacy, the
safety and pharmacokinetic profile of 3 led to FDA granting fast-
track IND status for clinical trials.[5]
Figure 2. Assorted ring size and annulated variants of inositols.
As continuation of our long standing interest[9a-e,g] in the
design of polycyclitols, we have now conceptualized a new entity
in the form of 1,2,3,4,5,6,7,8,9,10-decahydroxydecalin 13 (DHD),
in which each of the 10 carbon atoms of the decalin moiety
carries a hydroxyl group. This ensemble can also be viewed as
one in which two inositols are conjoined through a shared
common ring junction, a sort of ‘inosito-inositol’ and embody the
imprint of both the constituents and can be expected to exhibit
either augmented or new bioactivity attributes. Thus, depending
upon the choice of the co-joining inositol pair, a new series of
DHDs can be imagined and a few prototypical constructs, 13-15
are displayed in Figure 3.
Figure 1. Inositols 1-3 with promising bioactivity potential.
In view of the wide ranging therapeutic attributes of inositols,
particularly in the context of Alzheimer’s disease,[6] numerous
1
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22 was obtained via the intermediacy of epoxy tetrol 21
(Scheme 2). The dihydroxylation in this case was surprisingly
anti-Kishi rule, possibly occuring through the involvement of -
face oxygen functionality on the propellane bridge.
Figure 3. Newly conceptualized decahydroxydecalins (DHDs).
The attractive architecture of DHDs 13-15 held enough
traction to embark on their synthesis. An added incentive for this
undertaking was the observation that both hydrogen bonding
and hydrophobic interactions of inositols e.g. scyllo-3 are crucial
to its binding to Amotif and their modulation by switching on
additional hydrogen bonding and fine tuning of the hydrophobic
surface can enhance binding efficiencies (vide supra) with
implications in Alzheimer’s disease. In our view, constructs 13-
15 had the potential to measure up to such possibilities. With
this backdrop of purpose, we chose DHDs 13-15 as possible
targets for and intriguingly selected naphthalene, an aromatic
hydrocarbon as the key starting material.
In our synthetic endeavour towards racemic DHDs 13-15, it
was imperative to select a decalin based starting material which
had adequately distributed functionality for sequential,
differentiated, oxyfunctionalization manoeuvres, particularly at
C9 and C10 bridgehead positions. These considerations led to
the identification of isotetralin 16, a symmetrical, bicyclic skipped
triene, readily and efficiently available from naphthalene via
reductive dearomatization (Birch reduction), as the launch
pad.[10] Regioselective bromination of the tetra-substituted
bridgehead double bond in 16 followed by silver acetate
mediated acetolysis and hydrolysis led to the cis-diol 17 in good
yield. The diol 17 was internally protected as a cyclic carbonate
and a bromination-dehydrobromination was executed following
an adaptation of the pioneering Ginsberg protocol [11] to deliver
protected tetraene 18 bearing a propellane architecture. The
propellane framework of tetraene 18 was solicited in view of its
known proclivity towards face-selective reactivity under
stereoelectronic control. [12]
Scheme 1. Assembly of key decalin-diepoxide intermediate, 19.
In order to advance 22 towards the target DHD, it was
subjected to epoxide ring opening under various reaction
regimes. However, to our disappointment, the epoxide in 22
proved to be stubborn to ring opening and deployment of AcOH,
TFA combinations in water at variable temperatures, BF3-Et2O
etc proved ineffective. Energy minimized 3-D structure of
compound 22 showed that the approach of the external
nucleophile towards epoxide ring is hindered from the front as
well as back side and this probably is the reason for its reticence.
Our initial impulse was to attempt a direct shot at the target
through per-dihydroxylation and/or per-epoxidation (with each
epoxide serving as a surrogate for 1,2-diol) on tetraene 18 but
such attempts invariably led to intractable product profile,
pointing to a more calibrated step wise approach. Controlled
epoxidation of tetraene 18 with m-CPBA led to a diepoxide 19 in
high yield (91%) with epoxidation occurring from both the -
faces of the cyclohexadiene moiety, an outcome reminiscent of
the cycloadditions similar to hetero-propellanes.12 The
stereostructure of diepoxide 19 was secured through X-ray
crystal structure determination[13] (Scheme 1). However, diene-
diepoxide 19 resisted all further attempts at epoxidation and
therefore recourse was taken to an alternate tactic to amplify
oxyfunctionalization of tetraene 18.
After some exploratory experiments it emerged that the less
hindered -epoxide ring in 19, anti to the carbonate bridge could
be regio- and stereoselectively opened under mild acidic
conditions to furnish epoxydiol 20 in decent yield and its
stereostructure was established through single crystal X-ray
studies. In order to amplify the oxyfunctionalization pattern in 20
enroute to the target DHD, it was subjected to exhaustive cis-
dihydroxylation with OsO4/NMMO under improved conditions
reported by researchers at Upjohn.[14] Initially, formation of only
mono-dihydroxylated epoxy tetrol 21 was encountered (structure
confirmed by X-ray, Scheme 2). Prima facie this was quite
intriguing in the sense that the olefinic double bond adjacent to
the epoxide ring in 20 underwent preferential dihydroxylation
compared to the more widely explored allylic alcohol double
bond. However, when this dihydoxylation reaction was continued
for a longer duration (5 days) the desired hexahydroxy epoxide
Scheme 2. Synthesis of epoxy-hexahydroxydecalin (HHD), 22.
To alleviate the crowded steric environment around the
epoxide ring in hexahydroxy-epoxide 22,
a
carbonate
deprotection maneuver was implemented in the presence of
KOH/MeOH to break open the propellane architecture and
reveal the decalin moiety, bearing an annulated epi-inositol
framework 23. The stereostructure of the resulting octahydroxy-
epoxide 23 was secured through the single X-ray crystal
structure determination of the derived epoxy-hexaacetate 24
(Scheme 3). With access to octahydroxy compound 23, we were
tantalizingly close to the target DHD and only the epoxide
equivalence to a diol needed to be established. However, this
maneuver once again proved capricious and the epoxide ring in
23 could not be opened under a variety of conditions like
2
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aq.AcOH, TFA/H2O, BF3-Et2O etc. that the sensitive nature of
the polyhydroxylated substrate would permit (Scheme 3).
With the convenient availability of propellanic tetrol-diene
26, the stage was set for simultaneous dihydroxylation of both
the double bonds of hydroxy-allyl moieties present to deliver the
all-important octol 30. Indeed prolonged exposure (6 days) of 26
to cat. OsO4 and excess NMMO (3 eq.) resulted in the formation
of propellane based octahydroxy compound 30 in decent yield
and was purified by flash column chromatography on a reverse
phase column. Although the stereochemistry of the newly
installed dihydroxy groups in 30 could be predicted on the basis
of Kishi rules[16] but given its pivotal position, an unambiguous
proof of stereostructure was necessary. Thus, 30 was
transformed to the corresponding crystalline octa-acetate 31
following routine acetylation protocol and a single crystal X-ray
structure determination secured its formulation, (Scheme 5).
Finally, unraveling of the fully hydroxylated decalin moiety
embedded in hetero-propellane 30 was accomplished through
base mediated deprotection of the carbonate functionality to
deliver the long sought racemic DHD 13. It has not been
possible to either grow single crystals of 13 or a co-crystal with
suitable hosts so far but it was obtained as an amorphous white
solid, nicely depositing/coating the walls of the RB flask (see
picture) and was fully characterized spectroscopically (1H & 13
C
Scheme 3. Synthesis of epoxy-octahydroxydecalin (OHD), 23.
NMR, HRMS etc. See Supporting Information), Scheme 5. With
this first time acquisition of DHD, the stage is set for generating
stereochemical diversity and developing a chiral version of the
syntheses.
This late stage failure with seemingly routine epoxide ring
opening in 23 to deliver DHD, forced a retreat to the drawing
boards and the initial launch pad, the propellane based
diepoxide 19, Scheme 1. It was observed that under modified,
more acidic conditions and longer reaction time, 19 led to a (2:8)
mixture of tetracyclic ether 25 (resulting from intramolecular
epoxide opening) and tricyclic tetrol 26, Scheme 4. Both the
epoxide rings in 19 opened regioselectively and while two
intermolecular nucleophilic openings led to tetrol 26, tandem
inter- and intramolecular epoxide ring opening led to ether 25.
Stereostructures of tetrol 26 and tetracyclic ether 25 were
secured by conversion of the former to its crystalline tetra-
acetate 28 and X-ray crystal structure determination and of the
latter through deprotection of the carbonate moiety to crystalline
tricyclic ether tetrol 27 and X-ray studies, Scheme 4. Formation
of tetrol 26 was a significant, preparatory advance in the pursuit
of DHDs and the decalin moiety in it was liberated through
carbonate deprotection to deliver hexahydroxy decalin derivative
29 in excellent yield. Indeed, 29 can be visualised as ‘condurito-
conduritol’,
a
new construct in the rich chemistry of
conduritols.[15] In this context it may also be recalled that the
conduritols are considered as precursors of inositols, mimicking
sugars and exhibit wide ranging bioactivity [15] (Scheme 4).
Scheme 5. Synthesis of first racemic decahydroxydecalin (DHD), 13.
In-silico evaluation of inositols, 1-3 and DHD, 13
After successfully completing the synthesis of DHD 13, it
was of immediate interest to compare it with inositols (1-3) in
respect of inhibition of polymerization and fibril formation of
Athrough in-silico evaluation. Initially, we mapped the
molecular potential energy surface (MPES) of DHD 13 and
compared the values with those of bioactive inositols 1-3 to gain
some insights into the correlations between the molecular
structures and extent of binding to the protein. A marked
difference in terms of the specific distribution of positive and
negative potentials (-6.5 × 10-2 to + 6.5 × 10-2) was observed
between 1-3 and 13.[17] Whereas the positive and negative
surface potential in case of the former is diffused over the entire
surface, it is more pronounced and selectively distributed in the
case of 13 with one side of the molecule dominated by positive
potential and the other by negative potential (Figure 4). This
differential in potential distribution in 13 imparts dipolar character
to its surface and therefore it is expected to interact strongly and
more efficiently with target protein compared to simple inositols
1-3 with lesser number of hydroxyl groups.
Scheme 4. Synthesis of a condurito-conduritol, 29.
3
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Figure 4. Comparison of molecular potential energy surfaces (MPES,
calculated by B3LYP/6-31G(d) basis set) of inositols 1-3 and DHD 13.
To understand the implication of these variable potentials,
it was considered useful to assess the relative binding affinities
of the inositols (1-3) and DHD 13 towards the Alzheimer’s
disease related monomeric and hexameric A protein to provide
useful information about their binding potential. The binding
energy values indicate an increased binding potential for DHD
13 compared to inositols 1-3. Moreover, the subtle difference in
binding affinity values between monomeric and hexameric A
protein units further revealed that DHD 13 acts both as
polymerization inhibitor as well as exhibits the potential to
disrupt the protein fibrils (Figure 5).
Figure 5. Comparison of binding affinity values of inositols 1-3 and DHD, 13.
In the light of these observations, it was decided to probe
into the molecular interactions of inositols 1-3 and DHD 13 with
the concerned Alzheimer’s disease related monomeric and
hexameric Aprotein units through the tool of molecular
docking using ‘Autodock vina 1.1.2 program[18] and finally
LigPlot+ was used to plot and discern the binding interactions
between the target molecules and protein units.[19] Though the
nature of interactions and the amino acids involved in these
interactions (Gly29, Lys28 and Ser26) are by and large same in
inositols 1-3 and DHD 13 but the latter with more hydroxyl
groups showed increased number of hydrogen bonding (Asn27)
as well as hydrophobic interactions, (Figure 6). These in-silico
results indicate better profile of DHD 13 in stabilizing the
monomeric protein units thereby inhibiting polymerization and
also disrupting hexameric units.
Figure 6. Lig plots of inositols 1-3 and DHD, 13 showing interactions with
monomeric and hexameric A-protein units.
In conclusion, a racemic synthesis of a newly conceived
decahydroxydecalin (inosito-inositol) has been devised from
aromatic hydrocarbon naphthalene via
a
series of
sequentially executed oxyfunctionalization manoeuvres with
attendant regio- and stereocontrol. This approach should be
adaptable for diversity creation and syntheses of a host of
DHDs with variegated stereochemical footprint and
developing a chiral version. Initial indications from in-silico
evaluation of this newly accessed DHD through molecular
potential energy surfaces, relative binding affinities and
docking studies hold promise as
a disruptor of the
polymerization and fibril formation of protein implicated
in Alzheimer’s disease. Following on these indications, we
are currently scouting for suitable bio-essays and other
probes to evaluate the efficacy of DHD in Alzheimer’s and
diabetes.
4
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[13] G. Mehta, S. Sen, C. S. A. Kumar, Acta Cryst. 2013, E69, o1504-
o1505.
Acknowledgments
SR wishes to thank the School of Chemistry, University of
Hyderabad for hosting him. BAB acknowledges the grant support
from SERB, India (CRG/2019/005179). GM thanks Dr. Reddy’s
Research Laboratory (DRL) for the award of Dr. Kallam Anji Reddy
Chair (IIIM communication).
[14] V. Vanrheenen, R. C. Kelly, D. Y. Cha, Tetrahedron Lett. 1976, 17,
1973-1976.
[15] a) M. Balci, Pure Appl. Chem. 1997, 69, 97-104; b) M. S. Gultekin, M.
Celik, M. Balci, Curr. Org. Chem. 2004, 8. 1159-1186; c) J. Duchek, D.
R.; Adams, T. Hudlicky, Chem. Rev. 2011, 111, 4223-4258.
[16] a) J. K. Cha, W. J. Christ, Y. Kishi, Tetrahedron lett. 1983, 37, 3943-
3946; b) W. J. Christ, J. K. Cha, Y. Kishi, Tetrahedron lett. 1983, 37,
3947-3950.
Keywords: inosito-inositol 1• decahydroxydecalin 2 • condurito-
conduritol 3 • Amyloid- 4 • oxyfunctionalization 5
[17] a) A. D. Becke, Chem. Phys. 1993, 98, 1372-1377; b) P. J. Stephens,
F. J. Devlin, C. F. Chabalowski, M. J. Frisch, J. Phys. Chem. B 1994
98, 11623-11627.
,
References
[1] a) B. V. L. Potter, Nat. Prod. Rep. 1990, 7, 1-24; b) B. V. L. Potter, D.
Lampe, Angew. Chem. Int. Ed. Engl. 1995, 34, 1933-1972; c) Y. T.
[18] O. Trott, A. J. Olson, J. Comput. Chem. 2010, 31, 455-461.
[19] R. A. Laskowski, M. B. Swindells, J. Chem. Inf. Model. 2011, 51, 2778-
Chang, G. R. Rosania, S. K. Chung, Exp. Opin. Ther. Patents 2001
,
2786.
11, 45-59; d) R. F. Irvine, Nature Rev. Mol. Cell Biol. 2003, 4, 586-
590; e) S. B. Shears, S. B. Ganapathi, N. A. Gokhale, T. M. H.
Schenk, H. Wang, J. D. Weaver, A. Zaremba, Y. Zhou, Subcell
Biochem. 2012, 59, 389-412.
[2] a) N. W. Brown Jr., M. Alan, A. M. Marmelstein, D. Fiedler, Chem.
Soc. Rev. 2016, 45, 6311-6326; b) P. M. Rendle, F. Kassibawi, K. A.
Johnston, J. B. Hart, S. A. Cameron, A. Falshaw, G. F. Painter, K. M.
Loomes, J. Med. Chem. 2016, 122, 442-451. c) F. Cheng, L. Han, Y.
Xiao, C. Pan, Y. Li, X. Ge, Y. Zhang, S. Yan, M. Wang, J. Agric. Food
Chem. 2019, 67, 5957-5967.
[3] a) S. B. Shears, Biochem. J. 1989, 260, 313-324; b) S. Cockcroft, G.
M. H. Thomas, Biochem. J. 1992, 288, 1-14; c) T. Meyer, D. Holowka,
L. Stryer, Science 1998, 240, 653-656; d) J. Baillargeon, E. Diamanti-
Kandarakis, R. E. Ostlund, T. Apridonidze, M. J. Iuorno, J. E. Nestler,
Diabetes Care 2006, 29, 300-305; e) J. E. Nestler, V. Unfer, Gynecol.
Endocrinol. 2015, 31, 501-505; f) A. Gateva, V. Unfer, Z. Kamenov,
Gynecol. Endocrinol. 2018, 34, 545-550.
[4] a) K. Tanaka, S. Takenaka, K. Yoshida, Austin J. Clin. Neurol. 2015
,
2, 1040; b) M. Bizzarri, S. Dinicola, A. Bevilacqua, A. Cucina, Int. J.
Endocrinol. 2016, 2016, 27795708.
[5] a) J. McLaurin, M. E. Kierstead, M. E. Brown, C. A. Hawkes, M. H.
Lambermon, A. L. Phinney, A. A. Darabie, J. E. Cousins, J. E. French,
M. F. Lan, F. Chen, S. S. Wong, H. T. Mount, P. E. Fraser, D.
Westaway, P. St George-Hyslop, Nat. Med. 2006, 12, 801-808; b) K.
Ma, L. A. Thomason, J. McLaurin, Adv. Pharmacol. 2012, 64, 177-
212; c) S. Sinha, Z. Du, P. Maiti, F. G. l rner, T. Schrader, C. ang,
G. Bitan, ACS Chem. Neurosci. 2012, 3, 451-458; d) M. S. Butler, A.
A. B. Robertson, M. A. Cooper, Nat. Prod. Rep. 2014, 31, 1612-1661.
[6] a) J. McLaurin, R. Golomb, A. Jurewicz, J. P. Antel, P. E. Fraser, J.
Biol. Chem. 2000, 275, 18495-18502; b) S. Salloway, R. Sperling, R.
Keren, A. P. Porsteinsson, C.H. van Dyck, P. N. Tariot, S. Gilman, D.
Arnold, S. Abushakra, C. Hernandez, G. Crans, E. Liang, G. Quinn,
M. Bairu, A. Pastrak, J. M. Cedarbaum, Neurology 2011, 77, 1253-
1262.
[7] a) K. M. Sureshan, M. S. Shashidhar, T. Praveen, T. Das, Chem. Rev.
2003, 103, 4477-4503; b) Y. Sun, G. Zhang, C. A. Hawkes, J. E.
Shaw, J. McLaurin, M. Nitz, Biorg. Med. Chem. 2008, 16, 7177-7184.
[8] a) W. Hartmann, R. Steinmetz, Chem. Ber. 1967, 100, 217-222; b) F.
G. Cocu, Th. Posternak, Helv. Chim. Acta 1971, 54, 1676-1687; c) G.
Mehta, S. Pallavi, Chem. Commun. 2002, 2828-2829; d) G. Moura-
Letts, L. A. Paquette, Org. Chem. 2008, 73, 7663-7670; e) G. Mehta,
S. Pallavi, S. Katukojvala, Tetrahedron Lett. 2009, 50, 4519-4522.
[9] a) G. Mehta, S. S. Ramesh, Chem. Commun. 2000, 2429-2430; b) G.
Mehta, S. S. Ramesh, Tetrahedron Lett. 2001, 42, 1987-1990; c) G.
Mehta, S. S. Ramesh, Tetrahedron lett. 2002, 44, 3105-3108; d) G.
Mehta, S. S. Ramesh, M. K. Bera, Chem. Eur. J. 2003, 9, 2264-2272;
e) G. Mehta, S. S. Ramesh, Tetrahedron Lett. 2003, 44, 3105-3108; f)
Y. Kara, M. Balci, Tetrahedron 2003, 59, 2063-2066; g) G. Mehta, S.
Sen, Tetrahedron lett. 2010, 51, 503-507.
[10] E. Vogel, W. Klug, A. Breuer, Org. Synth. 1974, 54, 11-18.
[11] P. Ashkenazi, J. Kalo, A. Ruttimann, D. Ginsburg, Tetrahedron, 1977
34, 2161-2165.
,
[12] D. Ginsburg, Acc. Chem Res. 1974, 7, 286-293.
5
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Entry for the Table of Contents
Insert graphic for Table of Contents here.
Previously unknown entities in the form of 1,2,3,4,5,6,7,8,9,10-decahydroxydecalins (DHDs) have been conceptualized and the first
member of this class, an inosito-inositol, has been synthesized via a series of sequentially executed oxyfunctionalization manoeuvres
with attendant regio- and stereocontrol. The DHD accessed here has been subjected to preliminary in-silico evaluation with Aand is
expected to hold promise in Alzheimer’s therapeutics.
6
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