A unified approach to the salicylaldehyde containing polyketide natural products: Total synthesis of ent-pyriculol, ent-epipyriculol, ent-dihydropyriculol, ent-epidihydropyriculol, sordariol, sordarial, 12-methoxy sordariol, and agropyrenol

Article abstract of DOI:10.1016/j.tet.2020.131368

Many fungal metabolites are salicylaldehyde containing polyketide natural products and are often isolated from the fungus culture broth. These metabolites commonly exhibit phytotoxicity, however, some compounds exerted other biological activities including immunosuppressive activity. We have developed a unified synthetic strategy that provides easy access to ent-pyriculol, ent-epipyriculol, ent-dihydropyriculol, ent-epidihydropyriculol, trans-sordariol, trans-sordarial, 12-methoxy sordariol and agropyrenol.

Full text of DOI:10.1016/j.tet.2020.131368

Journal Pre-proof
A unified approach to the salicylaldehyde containing polyketide natural products:
Total synthesis of ent-pyriculol, ent-epipyriculol, ent-dihydropyriculol, ent-
epidihydropyriculol, sordariol, sordarial, 12-methoxy sordariol, and agropyrenol
Gaddam Mahesh, Jakka Raghavaiah, Gangarajula Sudhakar
PII:
S0040-4020(20)30523-8
https://doi.org/10.1016/j.tet.2020.131368
TET 131368
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 March 2020
Revised Date: 22 June 2020
Accepted Date: 24 June 2020
Please cite this article as: Mahesh G, Raghavaiah J, Sudhakar G, A unified approach to the
salicylaldehyde containing polyketide natural products: Total synthesis of ent-pyriculol, ent-epipyriculol,
ent-dihydropyriculol, ent-epidihydropyriculol, sordariol, sordarial, 12-methoxy sordariol, and agropyrenol,
Tetrahedron (2020), doi: https://doi.org/10.1016/j.tet.2020.131368.
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A Unified Approach to the Salicylaldehyde Containing Polyketide Natural Products: Total
Synthesis of ent-Pyriculol, ent-Epipyriculol, ent-Dihydropyriculol, ent-Epidihydropyriculol,
Sordariol, Sordarial, 12-Methoxy Sordariol, and Agropyrenol
Gaddam Mahesh,† Jakka Raghavaiah,†, ‡ and Gangarajula Sudhakar,*†, ‡
†Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical
Technology, Tarnaka, Hyderabad-500007, India
and
‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development
Centre (CSIR-HRDC) Campus, Ghaziabad-201002, UP, India
Email: gsudhakar@iict.res.in
Abstract
Many fungal metabolites are salicylaldehyde containing polyketide natural products and are
often isolated from the fungus culture broth. These metabolites commonly exhibit phytotoxicity,
1

however, some compounds exerted other biological activities including immunosuppressive
activity. We have developed a unified synthetic strategy that provides easy access to ent-
pyriculol, ent-epipyriculol, ent-dihydropyriculol, ent-epidihydropyriculol, sordariol, sordarial,
12-methoxy sordariol and agropyrenol.
Introduction
Certain organisms are essential in maintaining the ecological environment; for instance, fungi
involve in decomposing dead wood/carbohydrates-structural materials, while leaving dead
animals to bacteria. Several fungi live in symbiotic relations with plants, apparently the
adaptation of green plants to life on land.1 Conversely, fungi attack plants and cause huge loss to
the crops, and they are also known to produce host-specific secondary metabolites with
structurally distinctive and in certain cases exciting biological activities with a new mode of
action. A culture broth of the rice blast fungus, Pyricularia oryzae Cavara produced myriad
phytotoxic metabolites, and pyriculol (1) is the one isolated first in 1969 (Figure 1).2 Later,
structurally similar to pyriculol, epipyriculol (2),3 dihydropyriculol (3),4 epidihydropyriculol (4)3
and pyriculone (5)5 were isolated from the same fungus. Constitutional isomers (somewhat
varying the framework of pyriculol) such as pyricyculariol (6),6 dihydropyriculariol (7)7 and
pyricuol (8)8 were isolated from Magnaporthe grisea (Hebert) Barr (the perfect stage of
Pyricularia oryzae Cavara). In addition, monilidiol (9) and dechloromonilidiol (10) were
obtained in an attempt to isolate a self-growth inhibitor from benomyl-ressistant strains of cherry
brown rot fungus Monilinia fructicola.9 Sordariol (11) and sordarial (12) were isolated from
fungus Sordaria macrospora.10 Further, 12 was also isolated from Gelasinospora heterospora and
the absolute stereochemistry of it was determined by using Mosher’s method.11 Recently, Kong
et. al isolated 12-methoxy sordariol (13) along with four novel sordariol dimers from the same
2

fungus (Figure 1), and these dimmers (bisordariols A-C) exhibited potent ABTS radical cation
scavenging activities with 2-folds more potent than the positive trolox.12 The syn diol compound,
agropyrenol (14) was isolated from Ascochyta agropyrina var. Nana (a fungal pathogen of
Elitrigia repens) and the absolute configuration of it (14) was determined as 3´R,4´R by using
Mosher´s method,13 but very recently, this was a revised as 3´S,4´S by using biphenyl chiroptical
probes.14a
In fact these phytotoxic metabolites having salicylaldehyde-type moiety is a common feature.
They were isolated often from fungus culture broth and are trivially differ in structure. From the
activity standpoint, they are found to cause dark necrotic spots on rice leaves, a common
symptom of rice blast fungus and the most destructive blast disease of rice plant in Asian
countries.2 Pyriculol and epipyriculol inhibited significantly against a spore germination bioassay
while dihydropyriculol and epidydropuriculol showed no inhibition. However, dihydropyriculol
was found to prompt root elongation of rice seedlings.4 Monilidiol was active against
Staphylococcus aureus and also shown phytotoxicity to cherry leaves by inducing dark necrotic
spots.9 Sordariol was not phytotoxic towards rice roots, but it induced browning on the rice
leaves,10a and showed immunosuppressive activity.11 Agropyrenol (14) was tested for phytotoxic
activity,13 and its derivatives were examined for phytotoxic, antimicrobial, and zootoxic
activities. The results provided an important insights about the structure-activity relationship of
14.14b This group of salicylaldehyde-type polyketide metabolites having phytotoxic/growth
inhibitory activities as well as their potential use as novel natural herbicides12 naturally attracted
research groups to develop synthetic routes from the beginning of pyriculol’s discovery.
Watanabe group reported the first total synthesis of monilidiol (9) and dechloromonilidiol (10) in
a stereo-controlled fashion.15 Afterwards, the same group reported the first total synthesis and
3

absolute configuration of pyriculol (1)16a followed by all four stereoisomers of 1, including
epipyriculol (2).16b The synthesis of epipyriculol was accessed by Ley et. al starting from methyl
L-tartrate, and this feat was achieved somewhat in less number of steps (17 steps versus 20
steps).17 Before this, Kiyot et. al18 reported the first synthesis of pyricuol in an achiral version
(rac-8),18a and immediately thereafter asymmetric synthesis that revealed the absolute
configuration of pyriculol (8).18b The same group19 reported the first synthesis and absolute
configuration of pyriculariol (6),19a subsequently the synthesis of both enantiomers of pyricuol
(8) along with their plant growth inhibitory activity.19b The interest also aroused in biotechnology
groups to find the plausible biosynthesis and biosynthetic intermediates including genome
mining.20
OH
OH
OH
OH
CHO
CHO
OH
OH
OH
OH
OH
OH
Me
Me
Me
Me
OH
OH
OH
pyriculol (1)
OH
epipyriculol (2)
epidihydropyriculol (4)
dihydropyriculol (3)
OH
OH
R
OH
OH
R
CHO
CHO
CHO
O
OH
OH
Me
Me
C5H11
Me
OH
OH
R = CHO pyriculariol (6)
R = CH2OH: dihydropyriculariol (7)
O
OH
pyricuol (8)
R = Cl: monilidiol (9)
R = H: dechloromonilidiol (10)
pyriculone (5)
OH
R
OMe
OH
OH
OH
CHO
OH
OMe
OH
OH
OH
OH
Me
Me
Me
Me
R = CH2OH: trans-sordariol (11)
R = CHO: trans-sordarial (12)
OH
OH
OH
agropyrenol (14)
12-methoxy sordariol (13)
(E)-andytriol (
15
)
4

Figure 1. Salicylaldehyde-polyketide containing natural products (1-15) and synthetic targets 1-
4 and 11-14.
Almost a decade after the isolation of pyriculol (1), 2-methoxy-6-(3,4-dihydroxy-hepta-1,5-
denyl)benzyl alcohol (15, andytriol) was isolated from static culture of the fungus Aspergillus
variecolor.21 It is structurally very similar to dihydropyriculol (3) and the presence of additional
phenolic methyl ether in the salicylaldehyde moiety is the only difference. In 2002, varitriol and
varioxirane were isolated from fungus Emericella variecolor, interestingly it was proposed that
15 could be a biosynthetic precursor for these natural products.22 From the same fungus,
varioxiranols A-G were isolated recently and some of them found to exert inhibitory effects
against lipid accumulation at a dose of 10 µM.23
Because of our interest in the total synthesis of bioactive natural products,24 we have developed a
synthetic strategy to varitriol and varioxyrane based on the proposed biosynthetic pathway
commencing from Sharpless kinetic resolution (SKR) of α-hydroxy ester (±)-18.24f In this
approach, the epoxide obtained during the SKR was used in the synthesis of varitriol and
varioxirane, and the unreacted allylic alcohol (-)-18 was utilized in the synthesis of enantiomer
of andytriol (ent-15) as shown in figure 2A.24f After our synthesis, Gracza et al. reported the first
total synthesis of natural andytriol (15) from 2,3-O-isopropylidene
-ribose.25
D
5

Figure 2. Synthetic plan for enantiomer of dihydropyriculol (ent-3) from ent-(E)-andytriol 15
(unsuccessful) and from 19 and 17 (successful)
Given interest with these natural products, we envisaged that the cleavage of phenolic methyl
ether bond present in andytriol 15 could provide dihydropyriculol (3) and in the similar fashion
transformations would allow us to achieve other salicylaldehyde-polyketide natural products of
this class. However, our attempts in demethylating phenolic methyl ether of ent-15 under various
reaction conditions failed to produce the desired transformation, thwarting the access to ent-
dihydropyriculol (ent-3) from this approach (Figure 2A). This could be attributed to the binding
of hydroxyl groups (allylic and benzylic present in 15) with demethylating agent such as BBr3,
resulted in a complex mixture. Then, we had to embark on revising the strategy and have
contemplated replacing OMe group with an easily removable acetyl as a O-protecting group.
This can be taken off along with the other acetyl group (benzyl acetate), eluding the additional
deprotection step. Therefore the coupling of aromatic fragment 19 with ketophosphonate 17
(derived from 18 using (-)-DIPT in SKR), would provide compound 20 and subsequent
deacetylation should result in the ent-dihydropyriculol (ent-3) as shown in Figure 2B. Herein, we
6

report the synthesis of enantiomers of 1-4 and natural podes of 11-14 by developing a novel
strategy which is versatile and flexible in providing most of these salicylaldehyde-polyketide
natural products of choice.
Results and Discussion
Accordingly, the acetyl group protected aromatic fragment 19 was commenced from the
commercially available 2,3-dimethylphenol (R = H) which was subjected to acetylation with
Ac2O to give 21 in near quantitative yield (Scheme 1).26 Then, two step reaction sequence of
bromination/acetylation provided the compound 19 in 57% yield.27 Subsequently, compound 19
was coupled with ketophosphonate 17 to obtain an advanced intermediate 22 in 82% yield.
Scheme 1. Synthesis of 19 and 22
Having synthesized the intermediate 22, the stage was set to convert it to the target molecules,
shown in Schemes 2 and 3. Based on our previous results,24f the free α-hydroxy ketone 23
(obtained from 22 under silyl deprotection condition) was subjected to superhydride reduction to
furnish the anti-diol product 20 in 74% yield and 93:07 dr. Subsequently, treatment of 20 with
LAH cleaved both acetyls groups, obtaining the anticipated enantiomer of dihydropyriculol (ent-
3) in 64% yield. Then, compound 22 was subjected to NaBH4 reduction for syn-selectivity,
affording 24 in 93% yield and 87:13 dr. Then, deprotection of TBS in 24 using HF.py followed
7

by acetyl groups deprotection (of 25) using LAH resulted in enantiomer of epidihydropyriculol
(ent-4) in 78% yield (two steps).
Scheme 2. Synthesis of enantiomer of epihydropyriculol (ent-3) and enantiomer of
dihydropyriculol (ent-4)
Next, in order to obtain ent-pyriculol (ent-1) and ent-epipyriculol (ent-2), concealing of allylic
alcohols in 20 and 25 was necessary to perform oxidation on benzyl alcohol. In this direction,
acetonide protection was found to be suitable, therefore, 26 was prepared from reacting 20 with
2,2-DMP in the presence of catalytic amount of PTSA (Scheme 3). Then, acetyl groups were
removed under LAH reduction, obtaining 27 in a yield of 82%. Benzylic oxidation of 27 with
MnO2 provided the corresponding aromatic aldehyde 28 and subsequent acidic treatment with 1
N HCl furnished the desired product, enantiomer of pyriculol (ent-1) in 73% yield (two steps).
Following the same sequence of reactions, enantiomer of epipyriculol (ent-2) in 48% overall
yield was achieved from 25, via 29-31 as shown in Scheme 3.
8

Scheme 3. Synthesis of enatiomer of pyriculol (ent-1) and enantiomer of epipyriculol
(
ent
-2)
After achieving the synthesis of pyriculol series, we consider the synthesis of sodariol,
sordarial and agropyrenol. These natural products could be accessed from the
intermediate 32 following the similar sequence of reactions mentioned above. The
intermediate 32 would be obtained from a simple ketophosphonate 33 that in turn can be
derived from the easily available (-)-methyl -lactate (Figure 3).
L
Figure 3. Synthetic plan for 11, 12, and 14
9

In this direction, methyl -lactate was converted to keto-phosphonate 33 by following the
L
literature procedure (Scheme 4).28 Reacting keto-phosphonate 33 with aromatic aldehyde
19 afforded the advanced intermediate 32 in 84% yield, setting the stage to access the
desired molecules. Reaction of 32 with HF.py resulted in 34 that was subjected to super
hydride reduction to furnish the anticipated anti-diol product 35 in 63% yield and 86:14
dr. Subsequently, compound 35 was treated with DIBAL-H to yield trans-sordariol (11
)
in 74% yield. In order to achieve compound 12, both hydroxyls of 35 were protected as
TBS ether to obtain 36 in 96% yield. Treatment of diacetyl compound 36 with DIBAL-H
resulted in the free benzylic alcohol 37 which upon MnO2 oxidation afforded the
corresponding aldehyde 38 in 61% yield (two steps). Removal of both silyl groups
present in the 38 with HF.py furnished the desired natural product, trans-sordarial (12) in
71% yield. Next, compound 32 was subjected to NaBH4 reduction to provide syn-diol 39
(dr 91:09) which upon further silylation afforded compound 40 in 78% yield (two steps).
Subsequent DIBAL-H reduction on 40 provided acetyl free compound 41 that upon
benzylic oxidation afforded 42 (55% yield in two steps). Finally, removal of both silyl
groups delivered the agropyrenol (14) in 72% yield. The specific rotation of synthetic
agropyrenol ([α]25D: -43.0 (c 0.39, MeOH)) is resembled with the natural one [α]25D: -47.0 (c
(
0.5, MeOH)), supporting the revised absolute configuration reported recently.14a
10

OAc
O
O
O
ref 27
OMe
OMe
Me
OAc
OTBDMS
Me
KHMDS, THF
-78 °C-rt, 19
8 h, 84%
Me
P
OMe
OH
(-)-Methyl L-lactate
OTBS
33
32
O
OH
OAc
OAc
HF.Py
THF
0 C
12 h
79%
DIBAL-H
OH
OH
Me
LiEt3BH
OAc
OH
OAc
OH
32
THF, -78 °C
74%
Et2O, -78 C
OH
63%, dr 86:14
Me
Me
OH
35
34
O
trans-sordariol (11)
OH
OR
OH
HF.Py
TBSOTf
2,6-lutidine
CHO
°
CHO
THF, 0 C
MnO2
OR
OTBS
Me
35
10 h, 71%
OTBS
CH2Cl2, 0 C
96%
CH2Cl2
rt, 81%
OH
Me
Me
OH
OTBS
OTBS
38
36
: R = Ac
DIBAL-H, THF
0 °C, 76%
12
trans-sordarial (
)
37
: R = H
OH
OH
OAc
NaBH4
CeCl3
CHO
MnO2
DIBAL-H
OH
OAc
32
CH2Cl2, rt
88%
THF, 0 °C
MeOH
0 °C, 90%
dr 91:09
OR
Me
OTBS
Me
OTBS
63%
Me
TBSOTf
OR
42: R = TBS
OTBS
41
OR
HF.Py
2,6-lutidine
CH2Cl2, 0 °C
87%
39
: R = H
THF, 0 °C
12 h, 72%
40
: R = TBS
agropyrenol:
14
R = H (
)
Scheme 4. Synthesis of trans-sordariol (11), trans-sordarial (12), and agropyrenol (14)
Initially, we have isolated benzylmethyl ether containing product when attempted for
deacetylation of 20/24 using K2CO3 in MeOH. Earlier, a similar transformation was observed in
the literature, obtaining 3-(hydroxymethyl)-2-(methoxymethyl)phenol from (3-acetoxy-1,2-
phenylene)bis(methylene) diacetate in an attempt to saponify acetate groups in aqueous
methanol.16b Interestingly, this unexpected result became significant in this context as one of
11

these natural products, 12-methoxy sordariol (13), exists with benzyl methyl ether.12 Indeed,
reacting 35 with K2CO3 in MeOH furnished 12-methoxy sordariol (13) in 71% yield (Scheme 5).
Alternatively, this was also achieved by reacting 36 with K2CO3 in MeOH to get 43 and
subsequent silyl groups deprotection, obtained 12-methoxy sordariol (13) in 60% yield (over two
steps). The spectral data of the synthetic one resembles with data of the natural products.
Scheme 5. Synthesis of 12-methoxy sordariol (13)
Conclusions
We have accomplished the total synthesis of ent-pyriculol, ent-epipyriculol, ent-
dihydropyriculol, ent-epidihydropyriculol, sordariol, sordarial, 12-methoxy sordariol and
agropyrenol from a unified approach. The total synthesis of agropyrenol supported the revised
absolute configuration of this molecule. The synthesis of suitably protected aromatic fragment 19
facilitated the synthesis of these salicylaldehyde containing polyketide natural products of
choice. Coupling of this intermediate with appropriate ketophosphonate and further necessary
transformations can provide several natural products and their analogs for activity screening,
which is underway in our laboratory.
Experimental Procedures:
12

2,3-Dimethylphenyl acetate (21):25a To a solution of 2,3-dimethylphenol (50 g, 0.409 mol) in
CH2Cl2 (120 mL) at 0 ºC was added Et3N (114 mL, 0.819 mol) followed by dropwise addition of
Ac2O (58 mL, 0.6135 mol). After completion of the reaction in 10 min (monitored by TLC), ice-
cold water was added, and the aqueous layer was extracted by using CH2Cl2. The organic layer
was washed with brine solution, dried over Na2SO4, concentrated under reduced pressure. The
compound was purified by flash column chromatography to get compound 21 as yellow color
liquid (66.5 g). Yield: 99%; Rf = 0.6 (10% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3): δ 7.09
(dd, J = 7.7, 7.3 Hz, 1H), 7.03 (d, J = 7.3, 1H), 6.85 (d, J = 7.7, 1H), 2.31 (s, 3H), 2.28 (s, 3H),
2.07 (s, 3H); 13C{H} NMR (100 MHz, CDCl3): δ 169.5, 149.2, 138.5, 128.7, 127.5, 126.1, 119.4,
20.8, 20.1, 12.4; IR (Neat): νmax 2931, 2858, 1753, 1463, 1372, 1253, 1141, 1060, 974, 829, 812,
776, 664; HRMS: (ESI-TOF) m/z calcd for C10H13O2 (M + H)+ 165.0928, found 165.0910.
2-Acetoxy-6-formylbenzyl acetate (19): To a solution of 2,3-dimethylphenyl acetate 21 (5 gm,
30.48 mmol) in CCl4 (120 mL) was added NBS (16.1 gm, 91.46 mmol) and catalytic amount of
AIBN (0.2 equiv, ~1.0 gm, 6.09 mmol). Then, the reaction mixture was refluxed for overnight
(8-10 h), confirmed the formation of tribromo compound by 1H NMR. The reaction mixture was
filtered and washed with n-hexane for the elimination of excess NBS and other salts. The filtrate
was concentrated and dried over vacuum until it became a powder. Without further purification,
we proceeded to the next step.
To a solution of tribromo compound in anhydrous acetic acid (104 mL) was added NaOAc (8.5
gm, 103.7 mmol) portion-wise and refluxed for 36 h (the reaction mixture color turned to reddish
black). Then, the reaction mixture brought to rt, filtered with a pad of silica gel. AcOH was
evaporated on a rotary evaporator (bath temperature 70 ), diluted the reaction mixture with
EtOAc and filtered. To the filtrate was added 3 N HCl, kept it for 3 h stirring and extracted with
13

EtOAc (3 times). The organic layer was concentrated under reduced pressure, and the crude
product was purified by using silica gel column chromatography to get 19 as a colorless or light
1
reddish liquid (4.1 gm). Yield: 57%; Rf = 0.5 (30% EtOAc/hexanes); H NMR (400 MHz,
CDCl3): δ 10.30 (s, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.75 (t, J = 7.8, 1H), 7.36 (d, J = 7.8, 1H),
5.49 (s, 2H), 2.37 (s, 3H), 2.02 (s, 3H); 13C{H} NMR (125 MHz, CDCl3): δ 191.0, 170.5, 169.3,
150.2, 136.2, 130.0, 129.2, 129.0, 128.5, 55.7, 20.8, 20.7; IR (Neat): νmax 2924, 1761, 1581,
1468, 1369, 1207, 1183, 1090, 1061, 1009, 925, 864, 778, 730, 597; HRMS: (ESI-TOF) m/z
calcd for C12H13O5 (M + H)+ 237.07819, found 237.07575.
2-Acetoxy-6-((S,E,5R)-4-((tert-butyldimethylsilyl)oxy)-3-oxohepta-1,5-dien-1-yl)
benzyl
acetate (22): To a solution of β-Ketophosphonate 1724f (3.7 g, 11.01 mmol) in THF (30 mL) at
‒78 °C was added KHMDS (1.0 M in THF, 12.1 mL, 12.1 mmol) dropwise. After 30 min at ‒78
°C, compound 19 (3.89 g, 16.51 mmol) dissolved in THF (15 mL) was added and stirred for 12
h. Then, the reaction was quenched by the addition of the water, and the product was extracted
with EtOAc. The organic layer was washed with brine, dried over Na2SO4, and concentrated in
vacuum. The crude product was purified by using column chromatography on silica gel to give
α,β-unsaturated ketone 22 (4.2 g) as a colorless oil. Yield: 86%; Rf = 0.5 (20% EtOAc/hexanes);
[α]25D: = +42.72 (c 1.65, CHCl3); 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 15.9 Hz, 1H), 7.54
(d, J = 7.9 Hz, 1H), 7.40 (t, J = 7.9 Hz, 1H), 7.13 (dd, J = 1.0, 7.9 Hz, 1H), 7.11 (d, J = 15.9 Hz,
1H), 5.91 (ddd, J = 15.3, 6.7, 1.6 Hz, 1H), 5.50 (ddq, J = 15.3, 5.1, 1.6 Hz, 1H), 5.21 (ABq, J =
12.3 Hz, 2H), 4.66 (m, 1H), 2.34 (s, 3H), 2.02 (s, 3H), 1.73 (dd, J = 6.6, 1.5 Hz, 3H), 0.93 (s,
9H), 0.09 (s, 3H), 0.07 (s, 3H); 13C{H} NMR (75 MHz, CDCl3): δ 198.6, 170.5, 169.4, 150.1,
139.6, 137.3, 129.8, 128.8, 128.3, 127.4, 124.6, 124.3, 79.6, 56.9, 25.8, 20.8, 20.7, 18.3, 17.9, -
4.7, -4.9; IR (Neat): νmax 2924, 2853, 1766, 1733, 1637, 1579, 1468, 1371, 1224, 1202, 1184,
14

1046, 1025, 972, 753, 603; HRMS: (ESI-TOF) m/z calcd for C24H34O6Si (M + H) 447.2210,
found 447.2197.
2-Acetoxy-6-((R,1E,5E)-4-hydroxy-3-oxohepta-1,5-dien-1-yl)benzyl acetate (23): To a
solution of compound 22 (940 mg, 2.1076 mmol) in dry THF (12.6 mL) in a plastic vial at 0 ºC
was added a solution of HF. py (70% solution in py, 2.5 mL, 5.5291 mmol) dropwise using a
plastic syringe. Then, the reaction was allowed to rt and stirred for overnight. After completion
of the starting material, the reaction was quenched with saturated aq NaHCO3 solution by
maintaining pH neutral. Then, the aqueous layer was extracted with EtOAc, and the organic
layer was washed with water, brine, dried over Na2SO4, and concentrated under vacuum. The
crude compound was purified by flash column chromatography to get compound 23 (611 mg) as
a light yellowish liquid. Yield: 85%; Rf = 0.3 (50% EtOAc/hexanes); [α]25D: -52.88 (c 2.6,
CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J = 15.9 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.42
(t, J = 8.0 Hz, 1H), 7.17 (dd, J = 8.0, 1.0 Hz, 1H), 6.80 (d, J = 15.9 Hz, 1H), 6.03 (m, 1H), 5.44
(ddq, J = 15.2, 7.9, 1.6 Hz, 1H), 5.21 (s, 2H), 4.82 (d, J = 7.9 Hz, 1H), 3.89 (brs, 1H), 2.35 (s,
3H), 2.03 (s, 3H), 1.78 (dd, J = 6.6, 1.6 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 197.9,
170.4, 169.4, 150.2, 140.9, 136.5, 132.6, 130.0, 127.7, 127.4, 124.9, 124.8, 124.2, 77.7, 56.8,
20.8, 20.7, 18.0; IR (Neat): νmax 3449, 2954, 2926, 2854, 1770, 1738, 1468, 1374, 1224, 1202,
1185, 1091, 1046, 1024, 968, 863, 836, 777, 663; HRMS: APCI corona Full ms m/z: (M + Na)+
calcd for C18H20O6Na 355.1152; found 355.1139.
2-Acetoxy-6-((1E, 3S, 4R, 5E)-3, 4-dihydroxyhepta-1, 5-dien-1-yl) benzyl acetate (20): To a
solution of compound 23 (456 mg, 1.373) in dry ether (5.5 mL) at –78 ºC was added LiEt3BH
(2.06 mL, 1.0 M in THF, 2.0602 mmol). The reaction mixture was stirred at –78 °C for 10 min
and observed disappearing of starting material and formation of the complex on TLC.
15

Subsequently, the reaction was quenched with aq NH4Cl solution and stirred for a long time to
diminish the complex. The aqueous layer was extracted with EtOAc, and the organic layer was
dried over Na2SO4 and concentrated in vacuum. The extracted compound was purified by using
silica gel column chromatography (the complex was converted to product during column
purification) to afford anti-diol 20 (338 mg, dr 93:07 based on the 1H NMR) as a colorless liquid.
1
Yield: 74%; Rf = 0.3 (50% EtOAc/hexanes); [α]26D: +18.75 (c 0.23, CHCl3); H NMR (400
MHz, CDCl3) δ 7.37– 7.33 (m, 2H), 7.02 (m, 1H), 6.91 (dd, J = 15.7, 1.3 Hz, 1H), 6.03 (dd, J =
15.7, 6.7 Hz, 1H), 5.79 (m, 1H), 5.43 ddq, J = 15.2, 8.0, 1.6 Hz, 1H), 5.15 (s, 2H), 5.03 (ddd, J =
8.0, 6.7, 1.3 Hz, 1H), 4.90 (t, J = 8.0 Hz, 1H), 2.33 (s, 3H), 2.03 (s, 3H), 1.73 (dd, J = 6.6, 1.6
Hz, 3H); 13C{H} NMR (100 MHz, CDCl3): δ 170.7, 169.6, 150.08, 132.08, 130.2, 129.7, 129.0,
128.9, 124.6, 122.01, 75.6, 75.2, 57.5, 20.9, 20.8, 17.9; IR (Neat): νmax 3405, 2922, 2852, 1764,
1735, 1638, 1580, 1467, 1373, 1225, 1204, 1185, 1044, 1025, 968, 756, 604; HRMS: (ESI-TOF)
m/z: (M + Na)+ calcd for C18H22O6Na 357.1313; found 357.1308.
Enantiomer-dihdropyriculol (ent-3):3,4,20a To a solution of diacetyl compound 20 (37 mg,
0.110 mmol) in THF (1.1 mL) at 0 ºC was added LAH (12.6 mg, 0.332 mmol) in portion wise
and stirred at rt till completion of the starting material (3 h). The reaction was quenched (slowly
at 0 ºC) with saturated aq Na2SO4 and filtered through a sintered funnel. The aqueous layer was
extracted with EtOAc, and the organic layer was washed with brine solution, dried over Na2SO4,
and evaporated under reduced pressure. The crude product was purified by using silica gel
column chromatography to get the enantiomer of dihydropyriculol (ent-3) (19 mg) as a gummy
compound. Yield: 69%; Rf = 0.3 (80% EtOAc/hexanes); [α]24D: -7.33 (c 0.40, MeOH); 1H NMR:
(300 MHz, CD3OD + CDCl3) δ 7.10 (t, J = 7.9 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.91 (d, J =
15.8 Hz, 1H) 6.76 (d, J = 8.0 Hz, 1H), 6.10 (dd, J = 15.8, 6.4 Hz, 1H), 5.78 (m, 1H), 5.55 (m,
16

1H), 4.84 (ABq, J = 12.6 Hz, 2H), 4.24 (m, 1H), 4.12 (m, 1H), 1.74 (d, J = 6.4 Hz, 1H); 13C{H}
NMR (75 MHz, CD3OD + CDCl3): δ 157.25, 138.98, 132.29, 130.69, 130.46, 130.07, 124.91,
119.62, 116.39, 76.97, 76.85, 58.48, 19.07; IR (Neat): νmax 3375, 3019, 2918, 2855, 2360, 1639,
1609, 1569, 1450, 1328, 1310, 1237, 1193, 1163, 1081, 1045, 1009, 965, 845, 798, 750, 720,
666; HRMS: (ESI-TOF) m/z: (M + Na)+ calcd for C14H18O4Na 273.1099; found 273.1097.
2-Acetoxy-6-((1E,3R,4R,5E)-4-((tert-butyldimethylsilyl)oxy)-3-hydroxyhepta-1,5-dien-1-
yl)benzyl acetate (24): To a stirred solution of α,β-unsaturated ketone 22 (2.1 g, 4.706 mmol) in
MeOH (28.2 mL) was added anhydrous CeCl3 (5.2 g, 14.119 mmol) and allowed to stir for 30
min at rt. The reaction mixture was cooled to ‒50 °C and added NaBH4 (178 mg, 4.7064 mmol)
portion-wise and continued stirring for 20 min. After completion of the starting material
(monitored by TLC), the reaction was quenched by the addition of water at the same
temperature, slowly allowed to rt, and continued stirring for another 30 min. Then, the MeOH
was evaporated with rotary evaporated and poured the reaction mixture into ice-cold water and
extracted with EtOAc. Combined organic layers were washed with brine and dried over Na2SO4.
The crude compound was purified by using silica gel column chromatography to get pure
1
compound 24 (1.96 g, dr 87:13 based on the H NMR) as a colorless liquid. Yield: 93% (dr
1
87:13); Rf = 0.4 (30% EtOAc/hexanes); [α]24D: +7.53 (c 0.38, CHCl3); H NMR (400 MHz,
CDCl3) δ 7.37-7.29 (m, 2H), 6.99 (dd, J = 6.4, 2.7 Hz, 1H), 6.95 (dd, J = 15.8, 1.4 Hz, 1H), 6.09
(dd, J = 15.8, 5.7 Hz, 1H), 5.67 (m, 1H), 5.46 (ddq, J = 15.3, 7.6, 1.6 Hz 1H), 5.15 (s, 2H), 4.10
(t, J = 6.4 Hz, 1H), 3.97 (t, J = 6.9 Hz, 1H), 2.32 (s, 3H), 2.02 (s, 3H), 1.71 (dd, J = 6.4, 1.5 Hz,
3H), 0.91 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H); 13C{H} NMR (100 MHz CDCl3): δ 170.7, 169.6,
150, 139.8, 132.9, 130.6, 129.6, 129.3 ,127.8, 125.1, 124.4, 121.7, 77.6, 75.6, 57.5, 25.8, 20.9,
20.8, 18.1, 17.7, -3.8, -4.7; IR(Neat): ν max3406, 2954, 2926, 2854, 1770, 1738, 1468, 1374,
17

1224, 1202, 1185, 1091, 1046, 1024, 968, 863, 836, 777, 738, 673; HRMS: (ESI-TOF) m/z:
(M + Na)+ calcd for C24H36O6SiNa 471.2183; found 471.2173.
2-Acetoxy-6-((1E,3R,4R, 5E)-3,4-dihydroxyhepta-1,5-dien-1-yl)benzyl acetate (25): Syn-diol
25 (929 mg) as a colorless liquid was prepared from compound 24 (1.4 g, 3.125 mmol) following
the same procedure used for the synthesis of 23. Yield: 89%; Rf = 0.3 (30% EtOAc/hexanes);
1
[α]28D: +23.63 (c 0.16, CHCl3); H NMR (500 MHz, CDCl3) δ 7.34-7.30 (m, 2H), 7.0–6.96 (m,
2H), 6.10 (dd, J = 15.8, 6.0 Hz, 1H), 5.79 (m, 1H), 5.52 (ddq, J = 15.3, 7.0, 1.6 Hz, 1H), 5.15
(ABq, J = 12.3 Hz, 2H), 4.16 (t, J = 7.0 Hz, 1H), 3.99 (t, J = 7.0 Hz, 1H), 3.01 (brs, 1H), 2.78
13
(brs, 1H), 2.32 (s, 3H), 2.01 (s, 3H), 1.71 (dd, J = 6.5, 1.0 Hz, 3H); C{H} NMR (100 MHz,
CDCl3): δ 170.9, 169.7, 150.1, 139.5, 132.8, 129.9, 129.7, 129.5, 128.4, 125.2, 124.5, 121.9,
75.9, 75.5, 57.6, 20.9, 20.8, 17.9; IR (Neat): νmax 3405,2922, 2852, 2337, 1764, 1735, 1638,
1605, 1580, 1467, 1373, 1225, 1204, 1185, 1078, 1044, 1025, 968, 756, 604; HRMS: (ESI-TOF)
m/z: (M + Na)+ calcd for C18H22O6Na 357.1313; found 357.1308.
Enantiomer of epidihydropyriculol (ent-4):3 Enantiomer of epidyhydropyriculol ent-4 (31.6
mg) as a light yellow liquid was prepared from syn-diol 25 (48 mg, 0.01437 mmol) following the
same procedure used for the synthesis of ent-3. Yield: 88%; Rf = 0.3 (30% EtOAc/hexanes);
[α]24D: +19.67 (c 0.30, EtOH); 1H NMR (300 MHz, CDCl3 + CD3OD) δ 7.11 (dd, J = 7.8, 7.1 Hz,
1H), 6.99 (brs, 1H), 6.95 (d, J = 7.1 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 6.09 (dd, J = 15.8, 6.5 Hz,
1H), 5.80 (dq, J = 15.3, 6.4 Hz, 1H), 5.56 (ddq, J = 15.3, 7.1, 1.6 Hz, 1H), 4.83 (ABq, J = 13.0
Hz, 2H), 4.15 (m, 1H), 4.01 (t, J = 6.9 Hz, 1H), 1.74 (d, J = 6.3 Hz, 3H); 13C{H} NMR (75 MHz,
CDCl3+CD3OD) δ 155.8, 137.7, 131.2, 129.8, 129.1, 128.7, 128.4, 123.5, 117.7, 114.4, 75.7,
75.5, 56.4, 17.2
;
IR (Neat): νmax 3376, 3027, 1639, 1609, 1569, 1450, 1379, 1328, 1310, 1237,
18

1193, 1163, 1081, 1045, 1008, 965, 798, 749, 720; HRMS: (ESI-TOF) m/z: (M + Na)+ calcd for
C14H18O4Na 273.1099; found 273.1097.
2-Acetoxy-6-((E)-2-((4S,5R)-2,2-dimethyl-5-((E)-prop-1-en-1-yl)-1,3-dioxolan-4-
yl)vinyl)benzyl acetate (26): To a solution of diol compound 20 (115 mg, 0.3443 mmol) in
acetone (2.5 mL) was added 2,2-dimethoxypropane (DMP) (0.10 mL, 0.860 mmol) followed by
catalytic amount of PTSA (5.9 mg, 0.034 mmol) and the reaction was stirred for overnight at rt.
After completion of the starting material, the reaction was quenched with water, and the reaction
mixture was extracted with EtOAc. The organic layer was washed with brine solution, dried over
Na2SO4, and concentrated under reduced pressure. The compound was purified by flash column
chromatography to get 26 (105 mg) as a colorless liquid. Yield: 82%; Rf = 0.6 (20%
1
EtOAc/hexanes); [α]24D: -57.40 (c 0.15, CHCl3); H NMR (400 MHz, CDCl3) δ 7.38–7.32 (m,
2H), 7.01 (dd, J = 6.3, 3.0 Hz, 1H), 6.91 (dd, J = 15.7, 0.9 Hz, 1H), 6.05 (dd, J = 15.7, 7.4 Hz,
1H), 5.80 (m, 1H), 5.45 (ddq, J = 15.2, 8.3, 1.6 Hz, 1H), 5.15 (s, 2H), 4.75 (m, 1H), 4.65 (m,
1H), 2.33 (s, 3H), 2.03 (s, 3H), 1.72 (dd, J = 6.5, 1.6 Hz, 3H), 1.56 (s, 3H), 1.42 (s, 3H); 13C{H}
NMR (100 MHz, CDCl3) δ 170.7, 169.6, 150.0, 139.4, 131.2, 130.7, 129.7, 129.1, 126.7, 125.2,
124.7, 122.0, 108.8, 80.1, 79.4, 57.5, 28.1, 25.5, 20.9, 20.8, 17.9; IR (Neat): νmax 3019, 2927,
1735, 1469, 1372, 1214, 1186, 1048, 969, 929, 879, 743, 667; HRMS: (ESI-TOF) m/z:
(M + Na)+ calcd. for C21H26O6Na 397.1630; found 397.1621.
3-((E)-2-((4S,5R)-2,2-Dimethyl-5-((E)-prop-1-en-1-yl)-1,3-dioxolan-4-yl)vinyl)-2-
(hydroxymethyl)phenol (27): Compound 27 (17.1 mg) as oil was prepared from compound 26
(27.2 mg, 0.072 mmol) following the same procedure used for the synthesis of ent-3. Yield:
81%; Rf = 0.4 (30% EtOAc/hexanes); [α]24D: -26.9 (c 0.31, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 7.58 (brs, 1H), 7.16 (t, J = 7.9 Hz, 1H), 6.92 (d, J = 7.9 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.75
19

(d, J = 15.5 Hz, 1H), 5.92 (dd, J = 15.6 Hz, 7.3 Hz, 1H), 5.80 (dq, J = 15.5 Hz, 6.5 Hz, 1H), 5.45
(ddq, J = 15.5 Hz, 8.2 Hz, 1.6 Hz, 1H), 4.98 (s, 2H), 4.72 (dd, J = 7.3, 6.9 Hz, 1H), 4.64 (dd, J =
8.2, 6.9 Hz, 1H), 2.22 (brs, 1H), 1.73 (dd, J = 6.5 Hz, 1.6 Hz, 3H), 1.55 (s, 3H), 1.42 (s, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 156.5, 136.0, 132.1, 130.4, 129.0, 128.9, 126.7, 122.0,
118.9, 116.2, 109.0, 82.4, 81.8, 60.1, 27.1, 27.0, 17.9; IR (Neat): νmax 3331, 2985, 2921, 2852,
1711, 1679, 1582, 1467, 1373, 1279, 1254, 1228, 1165, 1050, 994, 965, 879, 838, 809, 787, 756,
666; HRMS: APCI corona Full ms m/z: (M + Na)+ calcd for C17H22O4Na 313.1410; found
313.1376.
2-((E)-2-((4S,5R)-2,2-dimethyl-5-((E)-prop-1-en-1-yl)-1,3-dioxolan-4-yl)vinyl)-6-
hydroxybenzaldehyde (28): Benzyl alcohol compound 27 (17.1 mg, 0.058 mmol) was taken in
dry CH2Cl2 (2.5 mL) and added MnO2 (51.2 mg, 0.589 mmol, 10 equiv) and stirred for overnight
(8-10 h) at rt. After completely disappearing the starting material (monitored by TLC), the
reaction mixture was filtered through a pad of silica gel, concentrated and purified by flash
column chromatography to give 28 as a viscous oil (14.4 mg). Yield: 85%; Rf = 0.5 (10%
1
EtOAc/hexanes); [α]23D: -29.9 (c 0.21, CHCl3); H NMR (500 MHz, CDCl3) δ 11.86 (s, 1H),
10.29 (s, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 15.7 Hz, 1H), 6.92-6.87 (m, 2H), 6.00 (dd, J
= 15.7, 6.7 Hz, 1H), 5.82 (dt, J = 13.0, 6.7 Hz, 1H), 5.45 (ddd, J = 15.7, 8.0, 1.6 Hz, 1H), 4.79 (t,
13
J = 6.7 Hz, 1H), 4.72-4.67 (m, 1H), 1.75 dd, J = 6.7, 1.6 Hz, 3H), 1.44 (s, 6H); C{H} NMR
(100 MHz, CDCl3) δ 195.1, 162.7, 141.8, 137.1, 132.9, 132.3, 127.4, 126.6, 118.8, 117.3, 109.2,
82.3, 81.2, 27.1, 26.9, 17.8; IR (Neat): νmax 2955, 2921, 2851, 1737, 1648, 1452, 1377, 1329,
1236, 1164, 1052, 965, 841, 756, 722 HRMS: (ESI/TOF) m/z: (M + H)+ calcd for C17H21O4
289.1436; found 289.1434.
20

Enatiomer of pyriculol (ent-1):16b-c Acetonide protected compound 28 was taken in a round
º
bottom flask and added THF (0.2 mL) via syringe. The reaction mixture was cooled to 0 C,
added 1N HCl (0.1 mL, 2 equiv), and stirred for 3 h at rt. The reaction mixture was quenched
with ice-cold water, and extracted with EtOAc. The organic layer was washed with brain
solution, dried over Na2SO4, and concentrated using rotary evaporator. The crude compound was
purified by using silica gel column chromatography to yield ent-1 (11.9 mg) as yellow crystalline
solid. Yield: 73%; MP: 96-98 ºC; Rf = 0.3 (50% EtOAc/hexanes); [α]25D: -39.9 (c 0.05, MeOH);
1H NMR (400 MHz, CDCl3): δ 11.85 (s, 1H), 10.31 (s, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.17 (d, J
= 15.6 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H), 6.11 (dd, J = 15.6, 5.7 Hz,
1H), 5.84 (m, 1H), 5.56 (ddq, J = 15.6, 7.2, 1.5 Hz, 1H), 4.38 (m, 1H), 4.23 (m, 1H), 2.27 (d, J =
4.5 Hz, 1H), 1.91 (d, J = 3.7 Hz, 1H), 1.75 (d, J = 6.5 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3)
δ 195.4, 162.7, 142.3, 137.0, 135.2, 130.6, 128.7, 126.6, 118.9, 117.1, 75.6, 74.7, 17.9; IR
(Neat): νmax 3374, 2921, 2852, 1642, 1610, 1569, 1451, 1329, 1310, 1238, 1193, 1164, 1082,
1009, 966, 924, 798, 751, 721; HRMS: (ESI/TOF m/z (M + Na) calcd for C14H16O4Na 271.0936;
found 271.0940.
2-Acetoxy-6-((E)-2-((4R,5R)-2,2-dimethyl-5-((E)-prop-1-en-1-yl)-1,3-dioxolan-4-
yl)vinyl)benzyl acetate (29): Compound 29 (216 mg) as a sticky oil was prepared from diol
compound 25 (250 mg, 0.748 mmol) following the same procedure used for the synthesis of 26.
Yield: 77%; Rf = 0.6(20% EtOAc/hexanes); [α]28D: +5.17 (c 0.29, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.40 (d, J = 7.9 Hz, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.01 (dd, J = 7.9, 1.0 Hz, 1H), 6.97
(d, J = 15.7 Hz, 1H), 6.08 (dd, J = 15.7, 6.9 Hz, 1H), 5.82 (m, 1H), 5.50 (ddq, J = 15.2, 7.8, 1.6
Hz, 1H), 5.13 (ABq, J = 12.1 Hz, 2H), 4.27 (m, 1H), 4.14 (t, J = 8.0 Hz, 1H), 2.32 (s, 3H), 2.02
(s, 3H), 1.73 (dd, J = 6.5, 1.6 Hz, 3H), 1.48 (s, 3H), 1.47 (s, 3H); 13C{H} NMR (100 MHz,
21

CDCl3): δ 170.7, 169.6,150.0, 139.4, 131.2. 130.7, 129.7, 129.1, 126.7, 125.2, 124.7, 122.0,
108.8, 80.1, 79.4, 57.5, 28.1, 25.5, 20.9, 20.8, 17.9; IR (Neat): νmax 3019, 2927, 1735, 1372,
1214, 1048, 969, 929, 743, 667; HRMS: (ESI-TOF) m/z calcd for C21H26O6Na (M + Na)+
397.1630, found 397.1621
3-((E)-2-((4R,5R)-2,2-dimethyl-5-((E)-prop-1-en-1-yl)-1,3-dioxolan-4-yl)vinyl)-2-
(hydroxymethyl)phenol (30): Compound 30 (123 mg) as a colorless sticky oil was prepared
from compound 29 (180 mg, 0.4781 mmol) following the same procedure used for the synthesis
of compound 27. Yield: 88%; Rf = 0.4 (30% EtOAc/hexanes); [α]28D: +21.87 (c 0.16 CHCl3); 1H
NMR (400 MHz, CDCl3) δ 7.85 (brs, 1H), 7.12 (t, J = 7.9 Hz, 1H), 6.94 (d, J = 7.5 Hz, 1H), 6.80
(d, J = 15.6 Hz, 1H), 6.79 (d, J = 7.5 Hz, 1H), 5.93 (dd, J = 15.6, 6.9 Hz, 1H), 5.82 (m, 1H), 5.48
(ddq, J = 15.2, 7.7, 1.6 Hz, 1H), 4.92 (s, 2H), 4.22 (ddd, J = 8.1, 6.9, 0.9 Hz, 1H), 4.12 (t, J = 8.0
Hz, 1H), 1.73 (dd, J = 6.6, 1.6 Hz, 3H), 1.47 (s, 3H), 1.46 (s, 3H); 13C{H} NMR (100 MHz
CDCl3): δ 156.4, 136.0, 132.1, 130.5, 128.9, 128.8, 126.7, 122.2, 118.9, 116.1, 109.0, 82.4, 81.8,
59.8, 27.1, 27.0, 17.9; IR (Neat): νmax 3331, 2985, 2921, 2852, 1711, 1605, 1582, 1467, 1373,
1279, 1254, 1228, 1165, 965, 838, 756, 627; HRMS: APCI corona Full ms m/z calcd for
C17H23O4 (M + H)+ 293.1747, found 293.1715.
2-((E)-2-((4R,5R)-2,2-dimethyl-5-((E)-prop-1-en-1-yl)-1,3-dioxolan-4-yl)vinyl)-6-
hydroxybenzaldehyde (31): Salicylaldehyde derivative 31 (68 mg) as a yellow color compound
was prepared from benzylic alcohol compound 30 (75 mg, 0.256 mmol) following the same
procedure used for the synthesis of 28. Yield: 92%; Rf = 0.5 (10% EtOAc/hexanes); [α]28
:
D
+26.66 (c, 0.07, CHCl3); 1H NMR (400 MHz, CDCl3) δ 11.84 (s, 1H), 10.28 (s, 1H), 7.45 (t, J =
8.0 Hz, 1H), 7.17 (d, J = 15.6 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 6.05
(dd, J = 15.6, 6.4 Hz, 1H), 5.85 (m, 1H), 5.51 (ddq, J = 15.2, 7.9, 1.6 Hz, 1H), 4.28 (ddd, 7.7,
22

6.4, 1.1 Hz, 1H), 4.14 (t, J = 8.2 Hz, 1H), 1.75 (dd, J = 6.5, 1.6 Hz, 3H), 1.48 (s, 3H), 1.47 (s,
3H); 13C{H} NMR (100 MHz, CDCl3): δ 196.1, 162.8, 141.9, 137.1, 132.9, 132.4, 127.5, 126.7,
118.9, 117.4, 117.3, 109.3, 82.4, 81.3, 27.1, 26.9, 17.9; IR (Neat): νmax 2955, 2921, 2851, 1737,
1648, 1611, 1452, 1377, 1312, 1236, 1164, 1052, 965, 882, 756, 722; HRMS: (ESI-TOF) m/z
calcd for C17H21O4 (M + H)+ 289.1436, found 289.1434.
Enantiomer of epipyriculol (ent-2):16c The enantiomer of epipyriculol (ent-2) (17.7 mg) as a
yellow color sticky compound was prepared from compound 31 (24 mg, 0.0827 mmol)
following the same procedure used for the synthesis of ent-1. Yield: 77%; Rf = 0.2 (50%
1
EtOAc/hexanes); [α]26D: +29.41 (c 0.08, CHCl3); H NMR (500 MHz, CDCl3) δ 11.85 (s, 1H),
10.29 (s, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 15.7 Hz, 1H), 6.90 (d, J = 7.2 Hz, 1H), 6.88
(d, J = 7.5 Hz, 1H), 6.08 (dd, J = 15.7, 5.5 Hz, 1H), 5.83 (dq, J = 15.7, 6.5 Hz, 1H), 5.55 (ddq, J
= 15.3, 7.3, 1.6 Hz, 1H), 4.22 (t, J = 5.7 Hz, 1H), 4.03 (t, J = 7.0 Hz, 1H), 2.78 (brs, 1H), 2.36
(brs, 1H), 1.74 (dd, J = 6.5, 1.5 Hz, 3H); 13C{H} NMR (100 MHz CDCl3): δ 195.3, 162.5, 142.1,
136.9, 136.5, 130.4, 129.2, 126.1, 118.7, 117.2, 116.9, 75.9, 75.0, 17.7; IR (Neat): νmax 3374,
3023, 2919, 2852, 1717, 1642, 1610, 1569, 1451, 1329, 1310, 1238, 1193, 1164, 1009, 966, 798,
751, 721; HRMS: (ESI-TOF) m/z (M + Na) + calcd for C14H16O4Na 271.0936, found 271.0940.
Dimethyl (S)-(3-((tert-butyldimethylsilyl)oxy)-2-oxobutyl)phosphonate (33):27 To a solution
of dimethyl methylphosphonate (5.1 g, 41.66 mmol) in dry THF (30 mL) under inert conditions
at -78 was added n-BuLi (17.3 mL, 27.77 mmol) dropwise and stirred for 45 min at same the
temperature. Next, (-)-methyl L-lactate (3.0 g, 13.88 mmol) in dry THF (25 mL) was cannulated
drop wise to the reaction mixture. After completion of the starting material (15 min), the reaction
was quenched with saturated aq NH4Cl at -78
and left it to rt. The reaction mixture was
extracted with EtOAc, and the organic layer was washed with brine solution, dried over Na2SO4,
23

and concentrated under reduced pressure. The product was purified by using silica gel column
chromatography to afford 33 as a light yellow color liquid (3.6 g). Yield: 93%; Rf = 0.3 (50%
EtOAc/hexanes); [α]26D: +9.3 (c 0.3, CHCl3); 1H NMR (400 MHz, CDCl3): δ 4.24 (q, J = 6.8 Hz,
1H), 3.81 (d, JP,H = 11.2 Hz, 3H), 3.78 (d, JP,H = 11.2 Hz, 3H), 3.37 (dd, JP,H = 21.2, JH,H = 14.9
Hz, 1H), 3.25 (dd, JP,H = 21.2, JH,H14.9 Hz, 2H) 1.32 (d, J = 6.8 Hz, 3H), 0.92 (s, 9H), 0.11 (s,
3H), 0.10 (s, 3H); 13C{H} NMR (100 MHz, CDCl3): δ 205.2 (d, JCP = 6.8 Hz), 74.8 (d, JCP = 3.2
Hz), 53.0 (d, JCP = 6.3 Hz) 52.9 (d, JCP = 6.3 Hz), 34.6 (d, JCP = 135.2 Hz), 25.7, 20.2, 18.0, -4.6,
-5.0; IR (Neat): νmax 2955, 2929, 2855, 1721, 1463, 1254, 1134, 1030, 938, 836, 809, 779, 663;
HRMS: (ESI-TOF) m/z calcd for C12H27O5NaSiP (M + Na)+ 333.1263 found 333.1270.
(S,E)-2-Acetoxy-6-(4-((tert-butyldimethylsilyl)oxy)-3-oxopent-1-en-1-yl)benzyl acetate (32):
β-Ketophosphonate 33 (3.5 g, 12.4 mmol) was dissolved in THF (30 mL) and cooled to ‒78 °C,
then 0.5 M KHMDS (14.8 mmol, 30mL) was added dropwise. After 30 min at ‒78 °C, 2-
acetoxy-6-formylbenzyl acetate (19) (14.89 mmol) dissolved in THF (20 mL) was cannulated
dropwise. Then the reaction mixture was left to rt, and run for 12 h at rt. After completion of the
reaction (monitored by TLC), it was quenched by the addition of water and extracted with
EtOAc. The organic layer was washed with brine, dried over Na2SO4, and concentrated by using
rotary evaporator. The crude product was purified by using silica gel column chromatography to
give α,β-unsaturated ketone 32 as a light yellow liquid (4.4 g). Yield: 84%; Rf = 0.6 (30%
EtOAc/hexanes); [α]26D: -38.02 (c 1.92, CHCl3); 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 15.8
Hz, 1H), 7.55 (d, J = 7.4 Hz, 1H), 7.40 (t, J = 7.4 Hz, 1H), 7.22 (d, J = 15.8 Hz, 1H), 7.13 (d, J =
7.4, 1H), 5.22 (ABq, J = 12.3, 16.6 Hz, 2H), 4.34 (q, J = 6.8 Hz, 1H), 2.33 (s, 3H), 2.01 (s, 3H),
1.36 (d, J = 6.8 Hz, 3H), 0.92 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H); 13C{H} NMR (125 MHz,
CDCl3): δ 201.5, 170.5, 169.4, 150.1, 139.7, 137.2, 129.9, 127.5, 124.5, 124.4, 123.7, 74.6, 56.8,
24

25.8, 21.1, 20.9, 20.7, 18.2, -4.7, -4.9; IR (Neat): νmax 2954, 2929, 2856, 1772, 1742, 1719, 1614,
1469, 1368, 1222, 1183, 1119, 1089, 1025, 941, 833, 779, 673; HRMS: (ESI-TOF) m/z calcd for
C22H32O6SiNa (M + Na)+ 443.1866, found 443.1873.
(S,E)-2-Acetoxy-6-(4-hydroxy-3-oxopent-1-en-1-yl)benzyl acetate (34): Compound 34 as a
light yellow colored liquid (0.790 gm) was prepared from compound 32 (1.42 g, 3.38 mmol)
following the similar procedure used for the synthesis of 23. Yield: 79%; Rf = 0.5 (50%
EtOAc/hexanes); [α]25D: +6.9 (c 1.81, CHCl3); 1H NMR (300 MHz, CDCl3): δ 8.11 (d, J = 15.8
Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 6.79 (d, J =
15.8 Hz, 1H), 5.21 (s, 2H), 4.56 (m, 1H), 3.68 (d, J = 5.2 Hz, 1H), 2.34 (s, 3H), 2.01 (s, 3H),
13
1.44 (d, J = 7.1 Hz, 3H); C{H} NMR (125 MHz, CDCl3): δ 220.8, 170.4, 169.4, 150.2, 140.9,
136.4, 130.0, 127.6, 124.9, 124.7, 123.9, 71.9, 56.8, 20.8, 20.7, 20.4; IR (Neat): νmax 3474, 2982,
1765, 1738, 1687, 1615, 1574, 1468, 1370, 1223, 1203, 1185, 1068, 1026, 979, 794; HRMS:
(ESI-TOF) m/z calcd for C16H18O6Na (M + Na)+ 329.1001, found 329.1006.
2-Acetoxy-6-((3R,4S,E)-3,4-dihydroxypent-1-en-1-yl)benzyl acetate (35): Anti-diol 35 as a
colorless liquid (250 mg, dr 86:14) was prepared from compound 34 (397 mg, 1.297 mmol)
following the procedure used for the synthesis of 20. Yield: 63%; Rf = 0.4 (50%
EtOAc/hexanes); [α]25D: +9.2 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3): δ 7.39 (m, 1H), 7.34
(t, J = 7.8 Hz, 1H), 7.03-6.96 (m, 2H), 6.17 (dd, J = 6.6, 15.8 Hz, 1H), 5.17 (ABq, J = 12.0, 16.2
Hz, 2H), 4.27 (m, 1H), 3.96 (m, 1H), 2.33 (s, 3H), 2.02 (s, 3H), 1.19 (d, J = 6.4 Hz, 3H); 13C{H}
NMR (100 MHz, CDCl3): δ 170.9, 169.6, 150.1, 139.3, 131.9, 129.8, 129.1, 125.2, 124.5, 122.0,
76.2, 70.3, 57.5, 20.9, 20.8, 17.8; IR (Neat): νmax 3429, 2923, 1764, 1736, 1560, 1468, 1371,
1225, 1204, 1168, 1024, 971, 930, 738; HRMS: (ESI-TOF) m/z calcd for C16H20O6Na (M + Na)+
331.1158 found 331.1162;
25

trans-Sordariol (11):10a-b To a solution of diacetyl compound 35 (31 mg, 0.1006 mmol) in dry
THF (1.5 mL) at -78 ºC was added an excess amount of DIBAL-H (1.0 M solution in toluene,
1.0 mL, 1.0064 mmol) dropwise. The reaction was slowly brought to rt and stirred untill the
completion of the starting material (̴ 1 h, monitored by TLC). The reaction was quenched (slowly
at 0 ºC) with saturated Rochelle salt (KNaC4H4O6) solution, and stirred at rt for 4-6 h. The
reaction mixture was extracted with EtOAc, and the organic layer was washed with brine
solution, dried over Na2SO4, evaporated under reduced pressure. The crude product was purified
by using silica gel column chromatography to get the trans-sordariol 11 as yellow sticky solid
1
(16.7 mg). Yield: 74 %; Rf = 0.4 (10% CH3OH/CHCl3); [α]26D: = +11.6 (c, 0.685, MeOH); H
NMR (400 MHz, CD3OD): δ 7.07 (t, J = 8.0 Hz, 1H), 7.02 (brd, J = 8.1 Hz, 1H), 7.0 (brd, J =
15.0 Hz, 1H), 6.72 (dd, J = 8.0, 1.2 Hz), 6.17 (dd, J = 15.7, 6.8 Hz, 1H), 4.78 (s, 2H), 4.07 (ddd,
J = 6.5, 5.0, 1.2 Hz, 1H), 3.77 (dq, J = 6.4, 6.5 Hz, 1H), 1.20 (d, 6.4 Hz, 3H); 13C{H} NMR (100
MHz, CD3OD): δ 157.3, 139.6, 132.5, 130.6, 129.7, 125.2, 118.9, 115.3, 78.0, 71.7, 56.5, 18.9;
IR (Neat): νmax 3321, 2923, 1638, 1580, 1467, 1274, 1074, 1014, 978, 648, 596; HRMS: APCI
corona Full ms m/z calcd for C12H16O4Na (M + Na)+ 247.0941, found 247.0917.
2-Acetoxy-6-((3R,4S,E)-3,4-bis((tert-butyldimethylsilyl)oxy)pent-1-en-1-yl)benzyl acetate
(36): To a solution of compound anti-diol 35 (52 mg, 0.168 mmol) in CH2Cl2 at 0 ºC was added
2,6-lutidine (0.07 mL, 0.675 mmol) followed by TBSOTf (0.07 mL, 0.337 mmol). Upon
completion of the reaction (15 min), it was quenched with ice-cold water and extracted with
CH2Cl2. The organic layer was washed with brine solution, dried over Na2SO4, and evaporated
under reduced pressure. The crude product was purified by using silica gel column
chromatography to afford 36 as a colorless liquid (86.2 mg). Yield: 96%; Rf = 0.6 (5%
EtOAc/hexanes); [α]23D: (-)11.4691, (c 1.05, CHCl3); 1H NMR (400 MHz, CDCl3): δ 7.39 (dd, J
26

= 1.1, 7.8 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 6.99 (dd, J = 1.3, 7.8 Hz, 1H), 6.86 (d, J = 15.8, 1H),
6.2 (dd, J = 5.9, 15.8 Hz, 1H), 5.16 (s, 2H), 4.09 (m, 1H), 3.76 (dt, J = 6.1, 11.2 Hz, 1H), 2.33 (s,
3H), 2.02 (s, 3H), 1.16 (d, J = 6.1 Hz, 3H), 0.92 (s, 9H), 0.87 (s, 9H), 0.10 (s, 3H), 0.05 (s, 3H),
0.05 (s, 3H), 0.02 (s, 3H); 13C{H} NMR (125 MHz, CDCl3): δ 170.7, 169.6, 150.0, 140.0, 136.3,
129.7, 126.4, 124.9, 124.1, 121.4, 78.2, 72.6, 57.3, 25.9, 20.9, 20.8, 19.8, 18.2, 18.1, -4.2, -4.4, -
4.5, -4.5; IR (Neat): νmax 2954, 2928, 2856, 1771, 1742, 1470, 1370, 1248, 1221, 1200, 1185,
1102, 1025, 971, 833, 810, 775, 672; HRMS: (ESI-TOF) m/z calcd for C28H48O6Si2Na 559.2887
(M + Na)+, found 559.2892;
3-((3R,4S,E)-3,4-Bis((tert-butyldimethylsilyl)oxy)pent-1-en-1-yl)-2-(hydroxymethyl)phenol
(37): Compound 37 as white crystalline solid (59 mg) was prepared from diTBS compound 36
(93 mg, 0.173 mmol) following the procedure used for the synthesis of 11. Yield: 76 %; M.P:
1
63-65 ºC; Rf = 0.4 (20% EtOAc/hexanes); [α]23D: (-)20.6014 (c 0.66, CHCl3); H NMR (400
MHz, CDCl3): δ 7.71 (brs, 1H), 7.15 (t, J = 7.8 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 6.79 (d, J = 7.8
Hz, 1H), 6.72 (dd, J = 1.6, 15.8 Hz, 1H), 6.11 (dd, J = 4.6, 15.8 Hz, 1H), 5.0 (s, 2H), 4.16 (ddd, J
= 1.6, 4.6, 4.7 Hz, 1H), 3.83 (dq, J = 4.7, 6.2 Hz, 1H), 1.04 (d, J = 6.2 Hz, 3H), 0.94 (s, 9H), 0.90
(s, 9H), 0.09 (s, 3H), 0.08 (s, 6H), 0.07 (s, 3H); 13C{H} NMR (125 MHz, CDCl3): δ 156.5,
137.3, 132.9, 128.9, 126.9, 121.6, 118.9, 115.5, 75.7, 71.5, 60.6, 36.6, 25.9, 18.2, 18.1, 17.4, -
4.5, -4.6, -4.6, -4.7; IR (Neat): ν max 3269, 2954, 2928, 2856, 1581, 1468, 1251, 1101, 990, 832,
810, 774, 672; HRMS: (ESI-TOF) m/z calcd for C24H45O4 Si2 (M + H)+ 453.28934, found
453.28509;
2-((3R,4S,E)-3,4-bis((tert-butyldimethylsilyl)oxy)pent-1-en-1-yl)-6-hydroxybenzaldehyde
(38): Aldehyde 38 as a colorless liquid (15.4 mg) was prepared from compound 37 (20 mg,
0.044 mmol) following the procedure used for the synthesis of 28. Yield: 81%; Rf = 0.6 (5%
27

1
EtOAc/hexanes); [α]25 : -11.7 (c 0.17, CHCl3); H NMR (400 MHz, CDCl3): δ 11.89 (s, 1H),
D
10.32 (s, 1H), 7.45 (t, J = 8.1 Hz, 1H), 7.05 (d, J = 15.8 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), 6.87
(d, J = 8.1 Hz, 1H), 6.17 (dd, J = 5.8, 15.8 Hz, 1H), 4.10 (m, 1H), 3.77 (dq, J = 5.6, 6.0 Hz, 1H),
1.17 (d, J = 6.0 Hz, 1H), 0.93 (s, 9H), 0.86 (s, 9H), 0.11 (s, 3H), 0.06 (s, 3H), 0.05 (s, 3H), 0.01
(s, 3H); 13C{H} NMR (100 MHz, CDCl3): δ 195.3, 162.8, 142.8, 138.7, 137.1, 124.7, 118.6,
117.3, 116.7, 78.1, 72.6, 25.9, 25.8, 20.0, 18.3, 18.1, -4.2, -4.4, -4.5; IR (Neat): νmax 2954, 2929,
2857, 1648, 1610, 1452, 1365, 1327, 1251, 1105, 1005, 834, 775, 722; HRMS: (ESI-TOF) m/z:
[M - H]+ calcd for C24H41O4Si2 449.2543; found 449.2557.
trans-Sordarial (12):10b,11 trans-Sordarial (12) as a yellow sticky solid (2.8 mg) was prepared
from compound 39 (8.0 mg, 0.0144) following the procedure used for the synthesis of 23. Yield:
1
71%; Rf = 0.3 (50 % EtOAc/hexanes); [α]19D: +16.43 (c 0.11 MeOH); H NMR (400 MHz,
CDCl3): δ 11.87 (s, 1H), 10.34 (s, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.20 (d, J = 15.7 Hz, 1H), 6.94
(d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.17 (dd, J = 15.7, 6.1 Hz, 1H), 4.35 (brs, 1H), 4.02
(m, 1H), 2.27 (bs, 1H), 1.99 (bs, 1H), 1.22 (d, J = 6.4, 3H); 13C{H} NMR (100 MHz, CDCl3): δ
195.23, 162.85, 142.16, 137.22, 134.81, 126.93, 118.91, 117.36, 75.82, 70.28, 17.79; IR (Neat):
νmax 3401, 3344, 2924, 1637, 1451, 1237, 1060, 721, 674, 663; HRMS: (ESI-TOF) m/z (M +
Na)+ calcd for C12H14O4Na 245.0781, found 245.0784
2-Acetoxy-6-((3S,4S,
E)-4-((tert-butyldimethylsilyl)oxy)-3-hydroxypent-1-en-1-yl)benzyl
1
acetate (39): Compound 39 as a colorless liquid (424 mg, dr 91:9 based on the H NMR)was
obtained from α,β-unsaturated ketone 32 (470 mg, 1.119 mmol) following the procedure used for
the synthesis of 24. Yield: 90%; Rf = 0.4 (20% EtOAc/hexanes); [α]26D: +4.7 (c 0.20, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 7.39 (dd, J = 7.9, 1.1 Hz, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.01 (dd, J =
7.9, 1.1 Hz, 1H), 6.98 (d, J = 16.0 Hz , 1H), 6.12 (dd, J = 15.8, 6.4 Hz, 1H), 5.18 (ABq, J = 12.1
28

Hz, 2H), 4.03 (m, 1H), 3.78 (m, 1H), 2.72 (d, J = 4.1 Hz, 1H), 2.34 (s, 3H), 2.03 (s, 3H), 1.21 (d,
J = 6.1 Hz, 3H), 0.92 (s, 9H), 0.12 (s, 3H), 0.11 (s, 3H); 13C{H} NMR (100 MHz, CDCl3): δ
170.7, 169.5, 150.0, 139.5, 133.3, 129.7, 128.3, 125.1, 124.2, 121.8, 72.0, 57.4, 25.8, 20.9, 20.8,
20.0, 18.0, -4.1, -4.7; IR (Neat): νmax 3429, 2956, 2925, 2854, 1772, 1739, 1576, 1465, 1374,
1249, 1224, 1185, 1094, 970, 836, 776, 673; HRMS: (ESI-TOF) m/z calcdfor C22H34O6NaSi
(M + Na)+ 445.2022 found 445.2024.
2-Acetoxy-6-((3S,4S,E)-3,4-bis((tert-butyldimethylsilyl)oxy)pent-1-en-1-yl)benzyl
acetate
(40): Compound 40 as a colorless liquid (290 mg) was prepared from compound 39 (264 mg,
0.625 mmol) following the similar procedure (2,6-lutidine (~0.3 mL, 2.50 mmol) and TBSOTf
(~0.3 mL, 1.25 mmol)) used for the synthesis of 36. Yield: 87%; Rf = 0.7 (5% EtOAc/hexanes);
1
[α]26D: -35.21 (c 1.98, CHCl3); H NMR (500 MHz, CDCl3): δ 7.39 (dd, J = 1.0, 7.8 Hz, 1H),
7.34 (t, J = 7.8 Hz, 1H), 6.98 (dd, J = 1.1, 7.8 Hz, 1H), 6.92 (dd, J = 1.5, 15.8 Hz, 1H), 6.30 (dd,
J = 4.0, 15.8 Hz, 1H), 5.15 (s, 2H), 4.30 (ddd, J = 1.8, 4.5, 4.5 Hz, 1H), 3.85 (dq, J = 4.5, 6.1 Hz,
1H), 2.33 (s, 3H), 2.01 (s, 3H), 1.05 (d, J = 6.1 Hz, 3H), 0.94 (s, 9H), 0.91 (s, 9H), 0.09 (s, 6H),
0.08 (s, 6H); 13C{H} NMR (125 MHz, CDCl3): δ 170.7, 169.6, 149.9, 140.6, 133.5, 129.7, 126.3,
124.8, 124.4, 121.2, 75.5, 71.5, 57.5, 25.8, 25.8, 20.9, 20.8, 18.1, 18.0, 17.3, -4.5, -4.6, -4.7, -4.8;
IR(Neat): νmax 2954, 2929, 2886, 2856, 1772, 1742, 1469, 1368, 1249, 1222, 1201, 1184, 1104,
1048, 1007, 970, 951, 834, 810, 775, 668; HRMS: (ESI-TOF) m/z calcd for C28H48O6Si2Na
559.2887 (M + Na)+, found 559.2892;
3-((3S,4S,E)-3,4-bis((tert-Butyldimethylsilyl)oxy)pent-1-en-1-yl)-2-(hydroxymethyl)phenol
(41): Compound 41 as a white crystalline solid (118 mg) was prepared from compound 40 (222
mg, 0.4141 mmol) following the same procedure used for the synthesis of 11. Yield: 63%; M.P:
1
60-61 ºC; Rf = 0.5 (20% EtOAc/hexanes); [α]26D: -28.76 (c 0.52, CHCl3); H NMR (400 MHz,
29