Model synthetic studies toward jiadifenin and majucin type seco-prezizaane natural products via a stereo- and enantioselective approach

Article abstract of DOI:10.1016/j.tetlet.2012.06.001

A concise stereo- and enantioselective approach to seco-prezizaane sesquiterpenoids, leading to the acquisition of two bicyclic fragments, is delineated.

Full text of DOI:10.1016/j.tetlet.2012.06.001

Tetrahedron Letters 53 (2012) 4320–4323
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Model synthetic studies toward jiadifenin and majucin type
seco-prezizaane natural products via a stereo- and enantioselective approach
Goverdhan Mehta a,b, , Harish M. Shinde a, R. Senthil Kumaran a
⇑
a Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
b School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A concise stereo- and enantioselective approach to seco-prezizaane sesquiterpenoids, leading to the
acquisition of two bicyclic fragments, is delineated.
Received 10 May 2012
Accepted 1 June 2012
Available online 12 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Natural product synthesis
Neurotrophic agents
Retro-Diels–Alder reaction
[3.3]-Sigmatropic shift
Intramolecular Horner–Wadsworth–
Emmons reaction
Stereoselective Luche reduction
seco-Prezizaane sesquiterpenoids have emerged as a growing
and diverse family of sesquiterpenoids, embodying complex poly-
cyclic architecture with varied oxygen functionalities.1 Interest-
ingly, the seco-prezizaane natural products have been
encountered only among the exotic and widely distributed Illicium
species and this resource has been extensively explored in recent
years by the group of Fukuyama among others.1
In Figure 1 are displayed several representative types among
the seco-prezizaane natural products. Among them, those belong-
ing to the jiadifenin core 1–2 and their biogenetic siblings of maju-
cin-prototype 3–7 hold instant appeal in view of their compact,
highly oxy-functionalized, cage-like molecular architecture and
the very special kind of bioactivity profile displayed by them.
Indeed, jiadifenin 1,1e jiadifenolide A 21h, and majucin derivatives
31h and 51e have been shown to exhibit neurotrophic activity by
promoting neurite outgrowth in primary cultures of rat cortical
First total synthesis of jiadifenin 1 was accomplished by the
group of Danishefsky2a,b and more recently Theodorakis et al.2c,e
have reported a synthesis of jiadifenin 1 as well as of related jiadif-
enolide 2. A model study toward the tricyclic core of 1 has also ap-
peared recently.2d Our group has been interested in the synthesis
of neurotrophically active natural products in general3 and of
seco-prezizaanes natural products in particular and we have re-
cently accomplished the total synthesis of merrilactone A3a,b and
of a
-minwanenone 8.3c As part of our continuing synthetic efforts
in the area, we have been drawn to jiadifenin and majucin type
natural products. Herein, we report a stereo- and enantioselective
approach toward the core bicyclic fragments present in them, rep-
resenting functionalized AB and BC rings. A very recent observa-
tion1i that even
a
simpler, truncated derivative like
jiadifenin-majucin type seco-prezizaane promoted impressive neu-
rite outgrowth at low M concentrations, lends relevance to our
7 of
l
neurons at 0.1–10
l
M concentration. It has also been observed that
endeavors disclosed in this Letter.
natural product jiadifenin 1 up-regulates the neurite outgrowth
activity of nerve growth factor (NGF), a natural neurotrophin.1,2b
These impressive bioactivity attributes, which have implications in
maintaining neuronal health and in addressing neurodegeneration
related disorders like Alzheimer’s, make seco-prezizaanes natural
products unique for exploring the chemical diversity space around
their scaffold and for mapping their therapeutic potential.2a–c
A retrosynthetic perspective on an approach to jiadifenin-maju-
cin frameworks (1 and 9) and leading to the functionalized frag-
ments 10 (AB rings) and 11 (BC rings) is displayed in Scheme 1.
A basic premise of this fragment based model conception was that
once the core strategies leading to the two segments 10 and 11
were successfully executed, they could be unified to target the nat-
ural products of this family. Our approach to both the fragments 10
and 11 emanated from a common chiral synthon (+)-12, readily
accessible from commercially available cyclopentadiene and p-
benzoquinone as per the protocols described earlier.4 A key feature
of our approach was the elaboration of the six-membered ring of
⇑
Corresponding author. Tel.: +91 4023010785; fax: +91 4023012460.
E-mail addresses: gmsc@uohyd.ernet.in, gm@orgchem.iisc.ernet.in (G. Mehta).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.001

G. Mehta et al. / Tetrahedron Letters 53 (2012) 4320–4323
4321
O
O
O
11
OH
OMe
O
O
O
O
HO
O
10
15
1
O
8
5
2
O
7
9
4
O
OH
O
O
OH
OH
OH
6
O
3
O
O
O
13
12
HO
HO
O
14
O
O
O
4: Jiadifenoxolane B
1: Jiadifenin
2: Jiadifenolide
3: Jiadifenoxolane A
O
O
O
HO
O
HO
O
R
O
O
O
HO
HO
OH
O
OH
O
O
OH
O
Me
OH
HO
HO
O
O
O
5: 2-Hydroxy-3,4-di-
8: Minwanenone
(R = α-Me / β-Me)
6: Dehydro-neomajucin
7: 2-Hydroxy-orneomajucin
hydroneomajucin
Figure 1. Representative types among seco-prezizaane sesquiterpenoids.
synthon (+)-12 into a stereochemically embellished ring ‘B’ of the
target natural products by harnessing the exo-face (convex face)
selectivity inherent to its tricyclic framework. In particular, the in-
tent was to secure the stereochemistry at the quaternary centers at
C4, C5, and C9 and concurrently install the requisite functionality.
1,4-Addition of vinyl group to the enone moiety of (+)-12 oc-
curred exclusively from its convex face to furnish 13 as a single
diastereomer.5 The vinyl group was introduced to serve as a latent
carboxylic acid equivalent at an appropriate stage. Kinetically con-
trolled methylation in 13 was regiospecific and furnished 14 with
protocol was implemented and the desired (+)-19 was realized, al-
beit in very modest yield. Stage was now set for the annulation of
the five membered ring A on (+)-19 and this was sought to be
achieved through an intramolecular Horner–Wadsworth–Emmons
(HWE) reaction.2b Consequently, (+)-19 was homologated to the b-
ketophosphonate (+)-20, Scheme 2. Intramolecular HWE in the
presence of sodium hydride delivered the desired bicyclic AB ring
fragment (+)-10 envisaged in the retrosynthetic theme, Scheme 1.
Termination of the surrogacy of the vinyl group as the carboxylic
acid equivalent and MOM deprotection in (+)-10 should lead to
good diastereoselectivity (b:
a
= 9:1), Scheme 2. A single-pot, dou-
the installation of
Attention was now directed toward the BC ring fragment 11
with the intent to demonstrate the feasibility of installing the
c-lactone moiety (ring C) on the bicyclic AB core.
ble hydroxyl-methylation on 14 was expectedly exo-face stereose-
lective and furnished a single diol (ꢀ)-15 in which the key C5
quaternary center and relative stereochemistry at C5 and C6 of
the natural product was correctly installed. The two hydroxyl
groups in (ꢀ)-15 were protected as MOM derivatives (ꢀ)-16 and
a retro Diels–Alder reaction released the functionalized cyclohexe-
none (ꢀ)-17, Scheme 2. Selective TBS deprotection in (ꢀ)-17 to
(ꢀ)-18 sets the stage for the installation of the key C9 quaternary
c
-
lactone moiety in a stereochemically secured manner. In this en-
deavor, dithiane was identified as the carboxylic acid surrogate.
Allylation of chiral synthon (+)-12 furnished (+)-21 in a regio-
and stereoselective manner.3c Conjugate 1,4-addition of dithiane
to (+)-21 occurred preferentially from the exo-face and the in situ
capture of the resulting enolate with methyl iodide delivered
(ꢀ)-22 as a single diastereomer having both the dithiane and the
methyl group cis-disposed on the convex face, Scheme 3. After con-
siderable trials,6,7 it was possible to induce dithiane unmasking in
(ꢀ)-22 using CAN under controlled conditions to furnish aldehyde
center with the required relative stereochemistry through
[3.3]-sigmatropic rearrangement. In the event, an Ireland-Claisen
a
(+)-23. On
a
-hydroxymethylation, (+)-23 directly delivered (ꢀ)-24
O
through concomitant lactol formation and concurrently secured
the C5 quaternary center, Scheme 3. PCC-oxidation of lactol (ꢀ)-
24 proceeded smoothly to deliver the lactone (ꢀ)-25. TBS-depro-
tection in (ꢀ)-25 to (+)-26 and further PCC oxidation proved quite
eventful and directly delivered (+)-28, bearing the requisite hydro-
OP
8
OH
10
HO
8
9
1
O
H
9
4
D
B
7
6
7
6
2
4
B
OH
A
B
5
O
5
O
A
12
O
O
OH
O
3
C
13
O 12
14
13
Me
C
14
xyl-c-lactone moiety, possibly through the intermediate chromate
O
OP
10
11
ester 27, Scheme 3. Retro-Diels–Alder reaction on (+)-28 proceeded
as planned to disengage the cyclopentadiene moiety and delivered
the bicyclic fragment (+)-29. Lastly, stereoselective hydride reduc-
tion on (+)-28 under Luche protocol8 led to 11 with required C7 rel-
ative stereochemistry corresponding to the BC ring fragment
identified in the retrosynthetic planning.
In summary, we have outlined a stereo and enantioselective
model study toward complex seco-prezizaane natural products
from a readily available Chiron. This study has led to the acquisi-
tion of key bicyclic AB and BC ring fragments in a concise and ster-
eoselective manner. Our results not only set the stage for executing
a general synthesis of seco-prezizaane family but offer avenues for
exploring the diversity space around these exceptionally bioactive
natural products. Efforts along these lines are currently underway
in our laboratory.
Majucin prototype 9
Scaffold control of
stereoselectivity
Scaffold control of
stereoselectivity
Ref 1e
O
OMe
O
HO
H
O
H
D
O
H
H
A
B
O
OH
O
TBSO
12
TBSO
12
C
O
Jiadifenin 1
Scheme 1. Retrosynthesis leading to model fragments.

4322
G. Mehta et al. / Tetrahedron Letters 53 (2012) 4320–4323
O
O
H
O
H
O
H
Ref.4
a
c
b
O
H
H
+
H
Me
TBSO
TBSO
TBSO
(+)-12
(−)−13
14
OTBS
OH
OMOM
O
MOMO
O
OMOM
O
d
e
Me
H
H
Me
OH
OMOM
TBSO
(−)-15
TBSO
(−)-16
Me
Me
MOMO
O
(−)-17
OMOM
OTBS
(−)-17
OMOM
OH
10
MOMO
O
8
MOMO
O
1
9
7
6
g
2
Me
h
f
i
Me
O
Me
4
5
3
12
O
OMOM
13 Me
(+)-10
OMOM
O
OMOM
MOMO
O
OMOM
14
OEt
P(O)(OMe)2
(−)-18
(+)-19
(+)-20
Scheme 2. Reagents and conditions: (a) Vinylmagnesium bromide, CuBrꢁSMe2, TMSCl, HMPA, THF, ꢀ78 to ꢀ60 °C, 3 h, 85%; (b) LHMDS, HMPA, MeI, THF, ꢀ78– 0 °C, 2 h, 77%;
(c) DBU, formalin, THF, 25 °C, 10 h, 60%; (d) MOMCl, DIPEA, DCM, 25 °C, 12 h, 88%; (e) Ph2O, 210 °C, 15 min, 90%; (f) TBAF, AcOH, THF, 0–25 °C, 2 h, 85%; (g)
triethylorthoacetate, propionic acid (0.2 equiv), 190–200 °C, 40 h, 30%; (h) CH3P(O)(OCH3)2, n-BuLi, THF, ꢀ78 °C, 1 h, 95%; (i) NaH, THF, reflux, 2 h, 92%.
H
d
a
c
O
b
O
O
O
H
H
H
H
Me
Me
H
TBSO
(+)-12
TBSO
(+)-21
TBSO
(−)-22
TBSO
(+)-23
S
S
O
O
O
O
O
e
g
f
H
H
O
H
O
H
Me
Me
Me
Me
O
Cr
O
TBSO
TBSO
HO
O
O
O
O
HO
O
HO
O
(−)-24
(−)-25
(+)-26
27
O
OH
8
O
Me
9
O
H
7
6
h
H
O
i
B
OH
O
B
4
Me
OH
B
C
O
5
O
O
O
C
O
O
HO
C
13
O 12
O
OH
14
O
O
(+)-29
(+)-28
(+)-29
11
Scheme 3. Reagents and conditions: (a) LiHMDS, allyl bromide, HMPA, THF, ꢀ20 °C, 2 h, 93%; (b)1,3-dithiane, n-BuLi, HMPA, THF, ꢀ78 °C, MeI, 3 h, 60%; (c) CAN, CH3CN, H2O,
30%; (d) DBU, formalin, THF, 25 °C, 14 h, 60%; (e) PCC, NaOAC, silica, 15 h, 70%; (f) TBAF, THF, 0–25 °C, 2 h, 80%; (g) PCC, NaOAC, silica, 0–25 °C, 1 h, 60%; (h) Ph2O, 200 °C,
10 min, 75%; (i) NaBH4, CeCl3, ꢀ78 °C, 68%.
Fellowship. This research was carried out at the Indian Institute
of Science, Bangalore. G.M. also acknowledges generous research
support from Eli Lilly and Jubilant Bhartia Foundations at the Uni-
versity of Hyderabad.
Acknowledgments
G.M. thanks CSIR, India for the award of Bhatnagar Fellowship.
H.M.S. and R.S.K. thank CSIR, India for the award of Research

G. Mehta et al. / Tetrahedron Letters 53 (2012) 4320–4323
4323
120.49, 96.51, 96.26, 72.20, 68.45, 64.22, 57.70, 55.34, 49.13, 25.79, 19.99, 18.06,
References and notes
-4.29, -4.39; HRMS(ES): m/z calcd for C21H38NaO6Si (M+Na): 437.2335, found:
437.2338. Compound 19: ½a D25
ꢂ
+51.7 (c = 0.6, CHCl3); IR (neat) 2933, 1736,
1. (a) Kuono, I.; Baba, N.; Hashimoto, M.; Takahashi, M.; Kawano, N.; Yang, C.-S.
Chem. Pharm. Bull. 1989, 37, 2448–2451; (b) Fukuyama, Y.; Shida, N.; Kodama,
M.; Chaki, H.; Yugami, T. Chem. Pharm. Bull. 1995, 43, 2270–2272; (c) Huang, J.-
M.; Yokoyama, R.; Yang, C.-S.; Fukuyama, Y. Tetrahedron Lett. 2000, 41, 6111–
6114; (d) Huang, J.-M.; Yokoyama, R.; Yang, C.-S.; Fukuyama, Y. J. Nat. Prod.
2001, 64, 428–431; (e) Yokoyama, R.; Huang, J.-M.; Yang, C.-S.; Fukuyama, Y. J.
Nat. Prod. 2002, 65, 527–531; (f) Yokoyama, R.; Huang, J.-M.; Hosoda, A.; Kino,
K.; Yang, C.-S.; Fukuyama, Y. J. Nat. Prod. 2003, 66, 799–803; (g) Don, X.-J.; Zhu,
X.-D.; Wang, Y.-F.; Wang, Q.; Ju, P.; Luo, S. Helv. Chim. Acta 2006, 89, 983–987;
(h) Kubo, M.; Okada, C.; Huang, J.-M.; Harada, K.; Hioki, H.; Fukuyama Org. Lett.
2009, 11, 5190–5193; (i) Kubo, M.; Kobayashi, K.; Huang, J.-M.; Harada, K.;
Fukuyama, Y. Tetrahedron Lett. 2012, 53, 1231–1235.
2. (a) Wilson, R. M.; Danishefsky, S. J. Acc. Chem. Res. 2006, 39, 539–549; (b)
Carache, D. A.; Cho, Y. S.; Hua, Z.; Tian, Y.; Li, Y.-M.; Danishefsky, S. J. J. Am. Chem.
Soc. 2006, 128, 1016–1022; (c) Trzoss, L.; Xu, J.; Lakoske, M. H.; Mobley, W. C.;
Theodorakis, E. A. Org. Lett. 2011, 13, 4554–4557; (d) Harada, K.; Imai, A.; Uto, K.;
Carter, R. G.; Kubo, M.; Hioki, H.; Fukuyama, Y. Org. Lett. 2011, 13, 4554–4557;
(e) Xu, J.; Trzoss, L.; Chang, W. K.; Theodorakis, E. A. Angew. Chem., Intl. Ed. 2011,
50, 3672–3676.
3. For synthetic work on diverse neurotrophic natural products from our group,
see: (a) Mehta, G.; Singh, R. Tetrahedron Lett. 2005, 46, 2079–2082; (b) Mehta, G.;
Singh, R. Angew. Chem., Int. Ed. 2006, 45, 953–955; (c) Mehta, G.; Shinde, H. M.
Tetrahedron Lett. 2007, 48, 8297–8300; (d) Mehta, G.; Maity, P. Tetrahedron Lett.
2007, 48, 8865–8868; (e) Mehta, G.; Bhat, B. A. Tetrahedron Lett. 2009, 50, 2474–
2477; (f) Mehta, G.; Maity, P. Tetrahedron Lett 2011, 52, 1749–1752; (g) Mehta,
G.; Maity, P. Tetrahedron Lett. 2011, 52, 1753–1756; (h) Mehta, G.; Maity, P.
Tetrahedron Lett. 2011, 52, 5161–5165; (i) Mehta, G.; Samineni, R.; Srihari, P.
Tetrahedron Lett. 2011, 52, 1663–1666; (j) Mehta, G.; Samineni, R.; Srihari, P.
Tetrahedron Lett. 2011, 53, 829–832.
4. (a) Takano, S.; Higashi, Y.; Kamikubo, T.; Moriya, M.; Ogaswara, K. Synthesis
1993, 948–950; (b) Nakashima, H.; Hiroya, K.; Taniguchi, T.; Ogasawara, K.
Synlett 1999, 1405–1406; (c) Konno, H.; Ogaswara, K. Synthesis 1999, 1135–
1140; (d) Mehta, G.; Islam, K. Synlett 2000, 1473–1475; (e) Mehta, G.; Shinde, H.
M. Chem. Comm. 2005, 3703–3705.
1047 cmꢀ1 1H NMR (300 MHz, CDCl3) d 5.89–5.71 (m, 3H), 5.19–5.13 (m, 2H),
;
4.57–4.53 (m,4H), 4.10–4.03 (m, 2H), 3.81 (d, J = 9.6 Hz, 1H), 3.65 (d, J = 9.3 Hz,
1H), 3.48–3.42 (m, 2H), 3.32 (s, 6H), 3.03 (d, J = 15.9 Hz, 1H), 2.59 (d, J = 15.3 Hz,
1H), 1.31 (s, 3H), 1.22 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 211.87,
170.88, 136.52, 130.45, 128.36, 117.83, 96.85, 96.56, 71.95, 70.29, 60.55, 55.48,
55.29, 51.26, 50.10, 48.87, 40.88, 19.66, 14.15. Compound 10: ½a D24
ꢂ
+107.1
(c = 0.8, CHCl3); IR (neat) 3080, 2930, 1719, 1698, 1606, 1045 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 6.12 (s, 1H), 5.88 (dd, J = 9.9 & 2.7 Hz, 1H), 5.81–5.69 (m, 1H),
5.59 (dd, J = 10.2 &1.8 Hz, 1H), 5.25–5.14 (m, 2H), 4.61–4.53 (m, 4H), 3.84 (d,
J = 9.6 Hz, 3H), 3.69 (d, J = 9.3 Hz, 3H), 3.44–3.28 (m, 8H), 2.82–2.77 (m, 2H), 2.24
(d, J = 17.1 Hz, 1H), 1.39 (s, 3H); 13C NMR (75 MHz, CDCl3) d 205.79, 183.86,
135.51, 131.19, 129.59, 128.64, 118.88, 96.94, 96.61, 73.22, 70.78, 55.70, 55.50,
52.69, 49.73, 49.28, 43.11, 22.24; HRMS (ES): m/z calcd for C18H26NaO5 (M+Na):
345.1678, found: 345.1677. Compound 22: ½a D24
ꢂ
-68.0 (c = 1.0, CHCl3); IR (neat)
2953, 1695, 1075 cmꢀ1 1H NMR (300 MHz, CDCl3) d 6.23–6.20 (m, 1H), 5.96–
;
5.93 (m, 1H), 5.71–5.57 (m, 1H), 5.10–5.03 (m, 1H), 4.74 (s, 1H), 4.10 (dd, J = 9.9
& 7.5 Hz, 1H), 3.13 (s, 1H), 2.91 (s, 1H), 2.86–2.68 (m, 4H), 2.46 (dd, J = 6.9 &
3.0 Hz, 1H), 2.13–2.06 (m, 2H), 1.98–1.74 (m, 2H), 1.48 (d, J = 8.7 Hz, 1H), 1.38
(d, J = 8.7 Hz, 1H), 1.28 (d, J = 6.3 Hz, 3H), 1.01 (s, 9H), 0.21 (s, 3H), 0.17 (s, 3H);
13C NMR (75 MHz, CDCl3) d 215.57, 137.32, 136.78, 134.03, 117.84, 69.88, 59.55,
53.76, 50.83, 49.48, 48.76, 47.74, 46.63, 46.55, 45.96, 33.28, 30.94, 26.89, 25.99,
18.21, 13.73, -3.44, -5.23; HRMS(ES): m/z calcd for C25H40NaO2S2Si (M+Na):
487.2137; found: 487.2135. Compound 25: ½a D24
ꢂ
-91.0 (c = 1.0, CHCl3); IR (neat)
3069, 1794, 1691 cmꢀ1 1H NMR (300 MHz, CDCl3) d 6.37–6.35 (m, 1H), 6.04–
;
6.01 (m, 1H), 5.71–5.57 (m, 1H), 5.15–5.10 (m, 2H), 4.16 (dd, J = 11.7 & 6.3 Hz,
1H), 3.97 (d, J = 9.1 Hz, 1H), 3.79 (d, J = 9.1 Hz, 1H), 3.28 (s, 1H), 3.03 (dd, J = 13.2
& 7.5 Hz, 1H), 2.82 (s, 1H), 2.55 (dd, J = 6.3 & 3.0 Hz, 1H), 2.34 (d, J = 11.1 Hz, 1H),
2.05 (dd, J = 12.9 & 8.1 Hz, 1H), 1.66–1.56 (m, 2H), 1.23 (s, 3H), 0.95 (s, 9H), 0.08
(s, 6H); 13C NMR (75 MHz, CDCl3) d 214.73, 175.22, 137.86, 134.92, 133.98,
119.09, 71.83, 67.08, 59.46, 55.55, 52.18, 50.47, 50.15, 45.50, 44.89, 25.84, 22.12,
18.06, -4.54, -4.99; HRMS(ES): m/z calcd for C23H34NaO4Si (M+Na): 425.2124;
found: 425.2125. Compound 28: ½a D21
ꢂ
+130.0 (c = 1.0, CHCl3); IR (neat) 3434,
1780, 1691 cmꢀ1 1H NMR (300 MHz, CDCl3) d 6.21–6.18 (m, 1H), 6.03–6.00 (m,
;
1H), 5.87–5.73 (m, 1H), 5.15–5.05 (m, 2H), 4.56 (s, 1H), 4.55 (d, J = 8.7 Hz, 1H),
4.18 (d, J = 9.0 Hz, 1H), 3.53 (s, 1H), 3.28 (s, 1H), 3.04 (d, J = 3.9 Hz, 1H), 2.68 (dd,
J = 15.0 & 7.5 Hz, 1H), 2.46 (dd, J = 15.0 & 7.5 Hz, 1H), 2.04 (s, 1H), 1.65 (d,
J = 12.9 Hz, 1H), 1.49 (d, J = 9.3 Hz, 1H), 0.98 (s, 3H); 13C NMR (75 MHz, CDCl3) d
210.64, 230.81, 172.46, 139.03, 138.19, 132.32, 119.03, 100.52, 80.13, 63.36,
59.46, 55.89, 50.40, 44.92, 44.36, 43.97, 13.70; HRMS(ES): m/z calcd for
5. All new compounds were characterized on the basis of their spectroscopic data
(IR, 1H, 13C, MS). Spectral data for some of the key compounds are as follows:
Compound 15: ½a 2D5
ꢂ
ꢀ28.3 (c = 0.6, CHCl3); IR (neat) 3553, 3071, 1686 cmꢀ1
;
1H
NMR (300 MHz, CDCl3) d 6.38–6.36 (m, 1H), 5.95–5.93 (m, 1H), 5.73–5.61 (m,
1H), 5.12 (dd, J = 9.9 & 1.8 Hz, 1H), 4.98 (dd, J = 16.8 & 1.8 Hz, 1H), 4.75 (dd,
J = 11.1 & 7.2 Hz, 1H), 4.31 (d, J = 9.6 Hz, 1H), 3.63–3.49 (m, 3H), 3.26 (s, 1H),
2.99 (bs, 1H), 2.88 (s, 1H), 2.71 (dd, J = 7.2 & 3.0 Hz, 1H), 2.21 (t, J = 10.5 Hz, 1H),
1.47 (d, J= 8.7 Hz, 1H), 1.39 (d, J = 8.7 Hz, 1H), 0.92 (s, 9H), 0.79 (s, 3H), 0.12 (s,
3H), 0.06 (s, 3H); 13C NMR (75 MHz, CDCl3) d 223.09, 138.74, 137.24, 134.95,
118.98, 73.15, 70.47, 70.04, 61.19, 53.16, 52.93, 52.10, 50.29, 48.62, 46.12, 26.04,
26.01, 19.72, 18.21, -3.87, -4.33; LRMS(ES): m/z calcd for C22H36NaO4Si (M+Na):
C
17H18NaO5 (M+Na): 325.1052; found: 325.1046. Compound 29: ½a D21
ꢂ
+33.6
(c = 1.1, CHCl3); IR (neat) 3446, 1790, 1690 cmꢀ1 1H NMR (300 MHz, CDCl3) d
;
6.89 (s, 1H), 5.83–5.70 (m, 1H), 5.34–5.15 (m, 2H), 4.98 (d, J = 8.7 Hz, 1H), 4.60
(s, 1H), 4.25 (d, J = 8.7 Hz, 1H), 3.20 (d, J = 6.6 Hz, 2H), 1.29 (s, 3H); 13C NMR
(75 MHz, CDCl3) d 196.64, 191.10, 170.63, 154.02, 134.95, 131.30, 120.25, 78.81,
73.76, 58.61, 33.89, 14.36.
415, found: 415. Compound 17: ½a D25
ꢀ98.3 (c = 1.2, CHCl3); IR (neat) 1670,
ꢂ
6. Recourse to our ‘oxides of nitrogen’ based convenient methodology6 for
unmasking the dithiane moiety, among others, were less successful.
7. Mehta, G.; Uma, R. Tetrahedron Lett. 1996, 37, 1897–1898.
8. Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226–2227.
1471, 1151, 1045 cmꢀ1 1H NMR (300 MHz, CDCl3) d 6.77 (s, 1H), 5.80–5.68 (m,
;
1H), 5.25–5.12 (m, 2H), 4.74–4.70 (m, 1H), 4.66 (s, 2H), 4.49 (d, J = 6.6 Hz, 1H),
4.46 (d, J = 6.6 Hz, 1H), 4.21 (s, 2H), 3.59 (d, J = 9.3 Hz, 1H), 3.48 (d, J = 9.6 Hz,
1H), 3.37 (s, 3H), 3.27 (s, 3H), 2.50 (t, J = 9.3 Hz, 1H), 1.06(s, 3H), 0.88 (s, 9H), 0.10
(s, 3H), 0.05 (s, 3H); 13C NMR (75 MHz, CDCl3) d 200.90, 148.18, 135.08, 134.20,