Friedelane triterpenoids: Transformations toward A-ring modifications including 2-: Homo derivatives

Article abstract of DOI:10.1039/c8nj00009c

Friedelin and its derivatives, commonly known as friedelane triterpenoids, exhibit potential biological effects ranging from antimicrobial to anticancer to anti-HIV. To modify the A-ring of the pentacyclic triterpenoid, various transformative scopes have been utilized. Herein, some simple unprecedented transformative protocols have been accomplished towards furnishing 42 (25 new) A-ring modified pentacyclic friedelane triterpenoids. It is worth noting that the modifications include the all-new 2-homo derivatives. The one-pot BF₃·OEt₂-mediated oxidative transformation of friedelin to yield friedel-3-enol acetate as the major product was one of the key reactions. A group of isomeric A-ring modifications was produced on the basis of simple transformations on suitable friedelane-based molecules. The syntheses of the novel 2-homofriedelanes were envisioned from the transformative reactions of the designed triterpenoid 3-chlorofriedel-2-ene-2-carbaldehyde, which was isolated as the major product from the reaction of friedelin with the novel Vilsmeier-Haack reagent. New A-ring modified derivatives were also obtained due to further interesting transformations of 3-chlorofriedel-3-ene, isolated as side products from the same reaction. Again, considering the scope of the 3-chloro-2-enal moiety associated with the A-ring of the triterpenoid, some heterocycle-linked- (bonded to C3) 2-homofriedelane triterpenoids were synthesized. Various common reaction strategies were employed on suitable substrates to finally achieve a series of C2,C3-; C3,C4- and C2,C3,C4-functionalized as well as 2-homofriedelane triterpenoids with just one to four efficient steps.

Full text of DOI:10.1039/c8nj00009c

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Friedelane triterpenoids: transformations toward A-ring
modifications including 2-homoderivatives†
Jayanta Das,# Antara Sarkar# and Pranab Ghosh*
Natural Products and Polymer Chemistry Laboratory, Department of Chemistry, North Bengal
University, Darjeelingꢀ734013, India
Abstract: Friedelin and its derivatives, commonly known as friedelane triterpenoids exhibit
potential biological effects ranging from antimicrobial to anticancer to antiꢀHIV. In urge to
modify the Aꢀring of the pentacyclic triterpenoid, various transformative scopes had been
utilized. Herein, some simple unprecedented transformative protocols have been accomplished
towards furnishing altogether 42 (25 new) Aꢀring modified pentacyclic friedelane triterpenoids.
Of note, the modifications include the allꢀnew 2ꢀhomoderivatives. Oneꢀpot BF3.OEt2ꢀmediated
oxidative transformation of friedelin to yield friedelꢀ3ꢀenol acetate as the major product was one
of the key reactions. A group of isomeric Aꢀring modifications were then resulted on the basis of
simple transformations on suitable friedelaneꢀbased molecules. The syntheses of the novel 2ꢀ
homofriedelanes were envisioned on the basis of the transformative reactions of the designed
triterpenoid 3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀcarbaldehyde which was isolated as the major product from
the reaction of friedelin with the novel VilsmeyerꢀHaack reagent. Aꢀring modified new
derivatives are also due to further interesting transformations of 3ꢀchlorofriedelꢀ3ꢀene, isolated as
a side product from the same reaction. Again, considering the scope of 3ꢀchloroꢀ2ꢀenal moiety,
associated with the Aꢀring of the triterpenoid, some heterocycleꢀlinkedꢀ (bonded to C3) 2ꢀ
homofriedelane triterpenoids were synthesized. Thus, various common reaction strategies were
employed on suitable substrates to achieve finally a series of C2,C3ꢀ; C3,C4ꢀ; and C2,C3,C4ꢀ
functionalized as well as 2ꢀhomofriedelane triterpenoids just within one to four efficient steps.
Keywords:Friedelin, pentacyclic triterpenoid, 2ꢀhomofriedelane triterpenoids,VilsmeyerꢀHaack
reaction
†Electronic Supplementary Information (ESI) available: copies of 1H and 13C NMR spectra of the
isolated products.

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#These authors contributed equally to this paper.
*Corresponding author. Fax: +91 353 2699 001; Tel: +91 353 2776 381; email: pizy12@yahoo.com
1. Introduction:
Friedelane (1) is a natural 6ꢀ6ꢀ6ꢀ6ꢀ6 pentacyclic triterpenoid (PT) alkane and, the PTs having the
same general skeleton are known as friedelane triterpenoids. The major fundamental compounds
of the triterpenoid group include friedelin (2), 2αꢀhydroxyfriedelanꢀ3ꢀone (cerin, 3) and friedelꢀ
2ꢀoxoꢀ3ꢀenol (not shown) which are, in fact the main constituents of the cork smoker wash solids
(Figure 1).1 More than 400 natural friedelane triterpenoids have been isolated till date. In their
review, Zhan et al. have summarized the natural sources of friedelane triterpenoids.2
Celastraceae, Hippocrateaceae, Euphorbiaceae, Flacourtiaceae, and Guttiferae are the families
of the plants where friedelanes were found most abundantly.2 Friedelin itself is bioactive3 and the
friedelane triterpenoids possess a wide spectrum of bioactivities ranging from antiꢀmicrobial to
antiꢀHIV to antiꢀcancer potential.4 To be specific, there are some naturally occurring highly
bioactive
friedelane
triterpenoids
viz.,
friedelaneꢀ3,15ꢀdioxoꢀ19αꢀol,5,6
celastrol,7
netzahualcoyone,8 demethylzeylasteral,9 etc. which makes this class of PTs truly more promising.
Total synthesis as well as biosynthetic routes of friedelin was aimed successfully.10 Majority
of the structural modifications of friedelin occurred in Aꢀring due to the ease of transformative
scopes, for ‘3ꢀketo’ is the only chemically active functional group in the molecule. A large
number of transformative attempts on various friedelane PTs were achieved which include
rearrangementꢀbased transformations,11 oxidation reactions (mediated by various oxidizing
agents viz., SeO2, NBS, mCPBA, OsO4, KOBut, LTA etc.),4l,4m,12 reduction reactions,13
photochemical transformations14 and others.15 Syntheses, transformations and rearrangements of
bromoꢀfriedelane triterpenoids were also noteworthy.11f,12d,13c,16 Moiteiro et al. have reported a
number of Aꢀring modified friedelane triterpenoids with their biological screening.1a,15e Our
laboratory has also attempted to furnish bioactive Aꢀring modified friedelane PTs.17 Again, Kang
et al. has achieved a novel process of direct amidation of sp3 CꢀH bonds, also applied to
friedelin.18
However, in spite of easy availability along with inꢀbuilt structural potentiality towards
bioactivity of the friedelane triterpenoids, friedelin has remained a bit striped towards the
transformative scopes, in comparison to other PTs. Thus in search of new facile transformative

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protocols as well as to produce more number of useful Aꢀring modifications, herein, we have
accomplished various unprecedented transformations toward furnishing altogether 42 numbers of
Aꢀring modified pentacyclic friedelane triterpenoids. These also include allꢀnew 2ꢀ
homoderivatives (31ꢀcarbonꢀbased) which were envisioned to explore a useful new series of
structural modifications contrary to all the earlier attempts with 30ꢀcarbonꢀbased Aꢀring
modifications. VilsmeyerꢀHaack reaction, a wellꢀknown transformative protocol for 2ꢀ
formylation of carbonyl compounds, was thus employed to utilize the carbonyl functionality of
friedelin to result the primary homoderivative 3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀcarbaldehyde (28).
Compound 28 was further transformed to furnish altogether 16 such new series of 2ꢀ
homoderivatives.
E
H
H
H
D
H
C
R1
O
A
B
1
2; R1= H, 3; R1= OH
Figure 1. Friedelane (1), friedelin (2) and cerin (3).
2. Results and discussion
The starting materials, friedelin (2) and cerin (3), were isolated from the petroleum ether extract
of the well known source Quercus suber bark. These were purified, and were characterized by
routine spectroscopic experiments along with the comparison of the known data (please follow
section 4.12). With the help of various known methodologies, transformations with friedelin
resulted some unprecedented reactions, whereas cerin resulted some useful isomeric known
derivatives. Hence incorporation of different functionalities directly into the friedelin skeleton
along with further simple transformations were found interesting to produce overall a number of
C2,C3ꢀ; C3,C4ꢀ; and C2,C3,C4ꢀ functionalized as well as 2ꢀhomofriedelane triterpenoids, the
details of which is discussed as follows.
2.1 Action of BF3.OEt2/Ac2O on friedelin: an unprecedented transformation

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Anticipating the accelerating and versatile effect of BF3.OEt2 in organic synthesis,19 friedelin was
attempted with the reagent along with acetic anhydride as the oxidant. A successful
unprecedented transformation was thus resulted in chloroform and at room temperature to isolate
three products analyzed as friedelꢀ2ꢀene (4, 7%), friedelꢀ3ꢀenol acetate (5, 42%; a new
compound) and friedelꢀ2ꢀoxoꢀ3ꢀenol acetate (6, 22%)(Scheme 1).
H
H
H
H
O
a
+
+
AcO
AcO
O
2
4 (trace - 7%)
6 (20- 32%)
5 (8- 60%)
Scheme 1. Treatment of BF3.OEt2/OAc2 on friedelin (a: BF3.OEt2, OAc2, CHCl3, r.t.,24h).
While evaluating the major product friedelꢀ3ꢀenol acetate (5) from the above reaction, we
found that the enol acetates, in general, are excellent reactive synthons for the functionalization
of the corresponding precursor carbonyl compounds and it is, indeed, remarkably evident from a
number of transformative reactions.20 As a consequence, people have tried to find out more facile
routes for the syntheses of enol acetates, and herein we have accomplished the isolation of
friedelꢀ3ꢀenol acetate as the major reaction product by an unprecedented BF3.OEt2ꢀmediated
oxidation of friedelin.
The reaction was conducted also with other potential Lewis acids viz., anhydrous aluminium
chloride, ferric chloride, titanium trichloride, magnesium chloride, zinc chloride and nickel
chloride at 100 mol% as well as in excess (5ꢀ10 eqv.) along with acetic anhydride; but no
transformation was achieved at all. The reaction was then tested by varying time and
temperature. Allowing the reaction for longer period of time yielded the enol acetate 5 better
(r.t., 48h, yield: 60%; and the yield of ketoꢀenol acetate 6 was not altered much) though change
in the condition from room temperature to reflux reduced the percentage yield of product 5
(reflux, 8h, yield: 8%) and increase that of 6 (reflux, 8h, yield: 32%). The reaction was also
attempted with different other oxidants viz., acetyl chloride, chloroacetyl chloride, benzoyl
chloride and benzyl bromide, instead of acetic anhydride. But none of them, in the same reaction
condition, were able to furnish the expected products.

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A probable mechanism was thus postulated for the formation of the major product enol
acetate 5. Utilizing the Lewis acidity of BF3.OEt2 and 4αꢀH (acidic, αꢀ to 3ꢀketo) of friedelin, 3ꢀ
enol trifluoroborate moiety 5a is proposed to be formed, which can then follow a transition state
5b involving an acetic anhydride molecule to result ultimately enol acetate 5 (Scheme 2).
H
#
H
H
H
-H+
-BF3OAc
-
F3B
O
O
O
F3B
F3B
O
AcO
H
2
O
5a
5
O
O
5b
O
O
Scheme 2. Probable mechanism for the formation of enol acetate 5.
2.2 Action of BF3.OEt2/Ac2O on friedelane-3-hydroxyimino (7) and friedelan-3β-ol (8)
Friedelaneꢀ3ꢀhydroxyimino (7, 88%, m.p. 289ꢀ291oC) and friedelaneꢀ3βꢀol (8, 72%, m.p. 290oC)
were prepared separately from friedelin following the usual method (both 7 and 8 were obtained
from friedelin (2) with the reaction of hydroxylamine hydrochloride and sodium borohydride
respectively; please follow experimental section). The effect of BF3.OEt2/Ac2O was then tested
on the oxime 7 and 3βꢀhydroxy compound 8 separately. Friedelaneꢀ3ꢀhydroxyimino (7) resulted
friedelꢀ3ꢀenol acetate (5, 18%) and friedelin lactam 9 (67%), whereas compound 8 furnished the
hydrocarbon friedelꢀ2ꢀene (4, 16%) and the acetate derivative of the starting material, friedelanꢀ
3βꢀacetate (10, 30%) (Scheme 3). The formation of the enol acetate from the oxime can be
figured as the deoxymination (to generate friedelin, 2) followed by fresh reaction with friedelin;
and the lactam 9 can be assumed easily to be formed following the Beckmann rearrangement on
the oxime.
H
H
a
O
+
5
HN
HON
(18%)
9 (67%)
7
H
H
a
+
4
AcO
(16%)
HO
8
10 (30%)

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Scheme 3. Action of BF3.OEt2/OAc2 on friedelaneꢀ3ꢀhydroxyimino (7) and friedelanꢀ3β−ol (8). a) BF3.
OEt2, Ac2O, CHCl3, RT, 24h.
2.3 Oxidation of friedel-3-enol acetate (5): acetoxy migration from C3 to C4
When friedelꢀ3ꢀenol acetate (5) was treated with CrO3/CH3COOH, it was interesting to note that
migration of the acetoxy group (ꢀOCOCH3) from C3 to C4 occurred to result a new compound
friedelꢀ3ꢀoxoꢀ4αꢀacetate (11, 41%, Scheme 4). To aim C3,C4ꢀepoxidation and/or probable
oxidative rearrangements, the enol acetate was treated with mꢀchloroperbenzoic acid (mCPBA).
On oxidation in this milder reaction condition the enol acetate was found to result three products
all having the acetoxy group migrated from C3 to C4. The products isolated were analyzed as
friedelꢀ3ꢀoxoꢀ4αꢀacetate and friedelꢀ3ꢀoxoꢀ4βꢀacetate (both new; 11, 12%; and 12, 35%
respectively), and friedelꢀ3βꢀolꢀ4αꢀacetate (13, 27%; another new compound) (Scheme 4).
Compound 11 is identical with the product obtained by chromic acid oxidation of enol acetate 5
and, compound 12 is the C4ꢀepimer of it (Scheme 4). Probable mechanisms for the 1,2ꢀacetoxy
migration towards the formation of compounds 11 and 12 are shown in Scheme 5.
H
H
H
i.
+
AcO
O
HO
AcO
AcO
11: 4α- (12%)
12: 4β- (35%)
13 (27%)
5
Scheme 4. mCPBAꢀOxidation of enol acetate: acetoxy migration from C3 to C4. (i. mCPBA/CH2Cl2, aq.
NaHCO3, r.t., 2h). Chromic acid oxidation (CrO3/CH3COOH, r.t., 2h) of enol acetate 5 furnished only 11
(41%).
H
H
H
-
AcO
HCrO4
-O
O
AcO
AcO
O
Cr
HO
O
O-
HO2CrO
5
-CrO3H-
mCPBA
O
H
H3C
C O
O
OAc
11/ 12
O
AcO
11
Scheme 5. Probable mechanism for the formation of 11 and 12.

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2.4 Access to 3,4-secofriedelane-3,4-diol (15), friedelan-3β-amin-4α-ol (17), Pachysandiol A
(18) and its 3α-epimer (19), and others
Friedelin was oxidized into the lactone 14 (81%) with mCPBA. The lactone was then treated
with NaBH4 to produce the 3,4ꢀsecofriedelaneꢀ3,4ꢀdiol (15, 72%) at a good yield. Thus the
sequence may be treated as an easy access to produce 3,4ꢀsecoderivatives selectively. Friedelin
was transformed into the enol acetate 5 followed by oxidation with mCPBA to result friedelꢀ3ꢀ
oxoꢀ4αꢀacetate, 11 (discussed previously). Then oximination of 11 with hydroxylamine
hydrochloride in pyridine resulted a new derivative friedelaneꢀ3ꢀoximinoꢀ4α−ol (16, 88%) which
on reduction with LiAlH4 finally yielded another new derivative friedelanꢀ3βꢀaminꢀ4αꢀol (17,
63%; Scheme 6).
H
H
H
i
ii
HO
O
HO
O
O
2
15 (72%)
14 (81%)
iii
H
H
H
v
iv
O
HON
H2N
AcO
11 (12%)
HO
16 (88%)
HO
17 (63%)
Scheme 6. i. mCPBA, CHCl3, reflux, 2h; ii. NaBH4, THF, reflux, 4h; iii) a. BF3.OEt2/ OAc2, CHCl3, r.t.,
24h; b. mCPBA, CH2Cl2, aq. NaHCO3, r.t., 2h; iv. NH2OH.HCl, py, 100oC, 4h; v. LiAlH4, dry THF,
reflux, 4h.
Pachysandiol A (18), structurally friedelaneꢀ2α,3βꢀdiol, is a natural compound available in
many plants,21 can also be achieved by the NaBH4 reduction of cerin (3, Figure 2). However, the
reduction of cerin with sodium in alcohol furnished a cisꢀdiol as the major product, the 3αꢀ
epimer of pachysandiol A, structurally friedelaneꢀ2α,3αꢀdiol (19, Figure 2). Acetylation of
friedelꢀ3βꢀolꢀ4αꢀacetate (13) with acetic anhydride in pyridine produced friedelaneꢀ3β,4αꢀ
diacetate (20, 95%). Friedelꢀ3ꢀoxoꢀ4αꢀacetate (11) was treated with KOH in aqueous MeOH to
produce friedelanꢀ3ꢀoxoꢀ4αꢀol (21, 84%). Compound 21 was reduced with NaBH4 to produce

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friedelaneꢀ3β,4αꢀdiol (22, 62%). Friedelin lactam 9 was reduced with lithium aluminium hydride
to yield a new compound sevenꢀmembered cyclic amine 23 (63%;). (Figure 2)
H
H
R1O
R2
RO
RO
18: R1= H, R2= β-OH (68%)
19: R1= H, R2= α-OH (62%)
26: R1= Ac, R2= β-OAc (97%)
20: R= Ac (95%)
22: R= H (62%)
H
H
H
RO
HN
23 (63%)
Y
O
HO
21 (84%)
24: R= Ac, Y= O (78%)
25: R= H, Y= NOH (95%)
Figure 2. Few more Aꢀring modified friedelane PTs (many of them are isomeric within the series).
Preparation: 18: from 3, NaBH4, CH2Cl2/MeOH, r.t., 4h; 19: from 3, Na/isopropanol, reflux, 2h. 20: from
13, Ac2O/ py, 100oC, 6h; 21: from 11, KOH, aq. MeOH, reflux, 30 min.; 22: from 21, NaBH4,
CH2Cl2/MeOH, r.t., 4h; 23: from 9, LiAlH4, dry THF, reflux, 6h; 24: from 3, Ac2O/py, 100oC, 6h; 25:
from 3, NH2OH.HCl/py, 100oC, 4h; 26: from 18, Ac2O/py, 100oC, 6h.
Considering the future evaluation scope of probable structureꢀactivity relationships (SAR) of
the different isomeric friedelane triterpenoids (modifications based on Aꢀring only), cerin (3,
itself isomeric to friedelanꢀ3ꢀoxoꢀ4αꢀol, 21) was allowed to have some simple transformations to
result few derivatives which are indeed isomeric to at least one of the prepared friedelane
triterpenoids based on the BF3.OEt2/Ac2Oꢀmediated transformative reaction. Thus, acetyl 24
(isomeric to 11 and 12), oxime 25 (isomeric to 16), diol 18 (isomeric to 22 and 19) and diacetate
26 (isomeric to 20) were prepared easily (please follow the experimental section). (Figure 2)
2.5 Action of Vilsmeyer-Haack reagent on friedelin: access to 2-homofriedelanes
Considering the useful scope of application of the VilsmeyerꢀHaack reagent22 (which uses
phosphorus oxychloride along with N,Nꢀdimethylformamide (DMF), we targeted friedelin as the
substrate, to prepare the 2ꢀ (and/or 4)ꢀformylated and associated derivatives. The derivatives
were indeed envisioned to be used to achieve a number of allꢀnew homofriedelane triterpenoids
by employing further simple transformative reactions.

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Thus first, when friedelin was treated with phosphorus oxychloride and DMF (please follow
experimental section), four new products isolated were characterized as 3ꢀchlorofriedelꢀ3ꢀene
(27, 12%), 3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀcarbaldehyde (28, 52%), friedelꢀ2ꢀenꢀ3ꢀolꢀ2ꢀcarbaldehyde
(29, 10%) and 3ꢀchlorofriedelꢀ2ꢀenꢀ4αꢀolꢀ2ꢀcarbaldehyde (30, 7%). (Scheme 7)
H
H
H
H
H
H
H
H
H
H
O
O
O
i
+
+
+
Cl
Cl
Cl
HO
O
HO
30 (7%)
2
27 (12%)
28 (52%)
29 (10%)
Scheme 7. Action of VilsmeyerꢀHaack reagent on friedelin (i. DMF/POCl3, CHCl3, reflux, 6h).
According to the previous reports of the action of VilsmeyerꢀHaack reagent on the
ketosteroids, besides the αꢀformylated major product, a chloroꢀene derivative was also isolated.23
Likewise, for friedelin as the substrate, it could furnish two isomeric chloroꢀenes viz., 3ꢀ
chlorofriedelꢀ2ꢀene and 3ꢀchlorofriedelꢀ3ꢀene (27); whereas in practice only the latter was
isolated that can be attributed due to the greater stability of the more substituted alkene.
However, on further simple transformative protocols, 27 resulted new Aꢀring modified friedelane
triterpenoids and, 28 furnished new 2ꢀhomofriedelanes having different functional/ active group
distributions as follows.
2.6 Further unprecedented A-ring modifications
Selenium dioxide, besides other transformative scopes, is a well known reagent for allylic
hydroxylation. When the reagent was employed on 3ꢀchlorofriedelꢀ3ꢀene (27), the 23ꢀmethyl of
the friedelane skeleton, an allylic one, was found to get oxidized into an aldehyde along with
simultaneous dechlorination to furnish a new compound friedelꢀ3ꢀeneꢀ23ꢀal (31, 56%).
Oxidation of 3ꢀchlorofriedelꢀ3ꢀene (27) with mCPBA was found to result the α−epoxidation
of the 3ꢀene functionality along with simultaneous dechlorination. Thus, the isolated product was
structurally a new derivative friedelaneꢀ3α,4αꢀepoxide (32, 56%). NBS is a reagent occasionally
used for allylic bromination although we were able to result selective Aꢀring aromatization of
steroids by using the same.24 Herein, while we aimed to achieve the corresponding 2 (and/or 4)ꢀ
bromo derivatives by employing NBS on 3ꢀchlorofriedelꢀ3ꢀene (27) it was our surprise to isolate

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an interesting new derivative Aꢀring aromatized 24ꢀNorfriedelꢀ1,3,5(10),6ꢀtetraene (33, 42%) as
the only product (Scheme 8). To note, there are actually a number of important biologically
active aromatized (or having their quinonoid structure)ꢀfriedelanes available in nature.25
H
H
H
H
i
H
Cl
27
O
ii
31 (56%)
iii
H
H
H
O
32 (56%)
33 (42%)
Scheme 8.i: SeO2/dioxane, 100oC, 36h; ii: mCPBA/CHCl3, reflux, 4h; iii: NBS/CHCl3, r.t., 24h.
2.7 2-Homofriedelanes including heterocycle-linked homofriedelanes
A series of ‘all new’ 2ꢀhomofriedelane triterpenoids were synthesized following two or more
sequential steps starting from friedelin. The key reaction, as is mentioned earlier, was the 2ꢀ
formylation of the triterpene by applying the novel VilsmeyerꢀHaack reagent. Then homo
derivative 28, the major product isolated was transformed into some more new derivatives to
enrich the friedelane triterpenoid series.
The 2ꢀformyl group of the 2ꢀhomoderivative 28 was transformed, by usual common
procedure, with hydroxylamine hydrochloride into the corresponding oxime, structurally 3ꢀ
chlorofriedelꢀ2ꢀeneꢀ2ꢀcarboxaldoxime (34, 98% after recrystallization, Scheme 9). Compound
28 was reduced with NaBH4 to result a new allylic alcohol, 3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀmethanol
(35, 92%). The 2ꢀmethanol friedelane derivative 35 was acetylated (with acetic anhydride) to
yield 3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀmethanol acetate (36; new derivative) quantitatively (Scheme 9).
Oxime 34 was allowed to reflux with anhydrous FeCl3 in dry DMF to isolate 3ꢀchlorofriedelꢀ2ꢀ
eneꢀ2ꢀcarboxamide (37, 58%), the Beckmann rearranged product probably via the 2ꢀnitrile

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derivative (Scheme 9). Thus, from friedelin, the interesting new derivative 37 was synthesized in
three steps only.
H
H
OHC
Cl
i
RO
Cl
28
35: R = H (92%)
36: R = Ac (98%)
ii
iii
O
H
H
iv
HON
Cl
H2N
Cl
34 (95%)
37 (58%)
Scheme 9.i. NaBH4, CHCl3/MeOH, r.t., 24h; ii. Ac2O/py, reflux, 1h; iii. NH2OH.HCl, pyridine, 100oC,
2h; iv. anh. FeCl3, dry DMF, reflux, 5h.
Compound 28 possesses two allylic positions available for further functionalization (at
C1 and C4), in what context selenium dioxide was employed to it for allylic hydroxylation.
Among the two allylic positions available, only the C4 was found to be hydroxylated, leaving
behind C1 completely. Thus the reaction of SeO2 with compound 28 furnished 3ꢀchlorofriedelꢀ2ꢀ
eneꢀ4αꢀolꢀ2ꢀcarbaldehyde (30, 65%; Scheme 10), which was a minor reaction product obtained
from the key reaction of friedelin with VilsmeyerꢀHaack reagent. In this context, it may be
concluded that the allylic C1 is much more reluctant towards hydroxylation, in comparison to the
allylic C4. Like compound 28, 3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀmethanol (35) also possesses two allylic
positions for further functionalization (at C1 and C4). The effort to transform 35 into the allylic
hydroxylated products by using selenium dioxide resulted only the C4αꢀhydroxylated 30 (62%)
where the primary allylic alcohol functionality of the reactant also got simultaneously oxidized
into the aldehyde group (Scheme 10). The 2ꢀformyl group of compound 30 was transformed into
the corresponding new oxime, structurally 3ꢀchlorofriedelꢀ2ꢀenꢀ4αꢀolꢀ2ꢀcarboxaldoxime (38,
97%; Scheme 10). Aldehyde 30 was reduced by using sodium borohydride into the
corresponding primary alcohol 39 (78%; a new compound), structurally 3ꢀchlorofriedelꢀ2ꢀenꢀ4αꢀ
olꢀ2ꢀmethanol (Scheme 10).

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H
H
OHC
Cl
R
i
Cl
HO
30 (65% from 28
62% from 35)
28: R= CHO
35: R= CH2OH
ii
iii
H
H
HO
HON
Cl
Cl
OH
39 (78%)
OH
38 (97%)
Scheme 10.i. SeO2, 1,4ꢀdioxane, 100oC, 24h; ii. NaBH4, CHCl3/MeOH, r.t., 24h; iii.NH2OH.HCl, py,
100oC, 2h.
The C3(sp2)ꢀCl of the homofriedelane 28 is susceptible to nucleophilic substitution
reactions thanks to the associative conjugated eneꢀformyl functionality. Thus, some suitable
nitrogen heterocycles of biological relevance were used as the nucleophiles to achieve the
resultants which are, indeed, the new group of heterocycleꢀlinked 2ꢀhomofriedelane derivatives
(40-45). The heterocycles used for the preparation of such interesting molecules are rather simple
and common, where we have used imidazole, benzimidazole and 1,2,3ꢀbenzotriazole as the
aromatic Nꢀheterocycles, and morpholine, piperidine and piperazine as the aliphatic Nꢀ
heterocycles. Of note, the attempted reactions under air produced poor yields (<10%) of the
desired products allowing compound 29 as the major yields (>75%) whereas under dinitrogen
atmosphere the yield of the heterocycleꢀlinked homofriedelane derivatives were found to be
satisfactory (Scheme 11).
O
O
N
H
H
H
H
H
H
H
H
H
O
i
i
Y
N
X
Cl
X
N
28
40: X= CH2 (72%)
41: X= O (70%)
42: X= NH (65%)
43: X= CH2, Y= H2 (72%)
44: X= CH2, Y= Ph (68%)
45: X= NH, Y= Ph (70%)
Scheme 11. Syntheses of aliphatic/ aromatic Nꢀheterocycleꢀlinked 2ꢀhomofriedelane derivatives (i. Nꢀ
Heterocycle, K2CO3, dry DMF, N2, 80oC, 3h).

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3. Conclusion
Syntheses of a number of Aꢀring modified friedelane triterpenoids including the allꢀnew 2ꢀhomo
derivatives have been accomplished following some unprecedented reaction protocols. Various
key routes for the modifications include a oneꢀpot BF3.OEt2/Ac2Oꢀmediated oxidative
transformation of friedelin into friedelꢀ2ꢀene (4), friedelꢀ3ꢀenol acetate (5, the major product) and
friedelꢀ2ꢀoxoꢀ3ꢀenol acetate (6); mCPBA oxidation of enol acetate (5) to achieve the migration
of C3 acetoxy group to C4; transformation of friedelin with VilsmeyerꢀHaack reagent to isolate
3ꢀchlorofriedelꢀ2ꢀeneꢀ2ꢀcarbaldehyde (28) as the major product. Besides, some other new useful
methodologies were established during various transformative attempts towards the Aꢀring
modifications. These include a twoꢀstep aromatization of friedelin by Nꢀbromosuccinimide, a
oneꢀpot dechlorination with simultaneous Cꢀ23 oxidation, and selective 4αꢀhydroxylation with
simultaneous oxidation of allylic alcohol by selenium dioxide. Thus overall, synthetically useful
derivatives such as friedelꢀ3ꢀenol acetate (5); friedelꢀ2ꢀoxoꢀ3ꢀenol acetate (6); friedelꢀ3ꢀoxoꢀ
4(α/β)ꢀacetate (11/12, and their diol derivatives); friedelanꢀ3βꢀolꢀ4αꢀacetate (13); 3,4ꢀsecodiol
15; 3βꢀaminoꢀ4αꢀol 17; 3ꢀchlorofriedelꢀ2ꢀenꢀ4αꢀolꢀ2ꢀcarbaldehyde (30); 2ꢀcarboxamide 37; 3ꢀ
chlorofriedelꢀ2ꢀenꢀ4αꢀolꢀ2ꢀmethanol (39); etc., were found very much effective to enrich the Aꢀ
ring modifications of friedelane triterpenoids in a few steps starting from friedelin. On the other
hand, as C3(sp2)ꢀCl of the homofriedelane 28 is susceptible to nucleophilic substitution reactions
thanks to the associative conjugated eneꢀformyl functionality, some suitable nitrogen
heterocycles of biological relevance were used as the nucleophiles to achieve the resultants
which are, indeed, the new group of heterocycleꢀlinked (to C3 of friedelanes) 2ꢀhomofriedelane
derivatives. We believe to use these friedelane triterpenoids for future biological applications as
well as to explore more interesting and useful multifunctionalized derivatives of the particular
class of pentacyclic triterpenoids. Thus, following few simple steps starting from friedelin, it
rendered possible easily to produce a number of C2,C3ꢀ; C3,C4ꢀ; and C2,C3,C4ꢀ functionalized
as well as 2ꢀhomofriedelane triterpenoids.
4. Experimental
4.1 General:

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Melting points were measured in open capillary methods and were uncorrected. 1H NMR and 13C
NMR spectra were recorded on Brucker Avance 300MHz FTꢀNMR spectrometer using 5 mm
BBO probe. CDCl3 or DMSOꢀd6were used as solvent and TMS as reference material. Data are
presented as follows: chemical shift ꢀin ppm on the scale relative to δTMS = 0; coupling constantꢀ
J/Hz. Infrared spectra were recorded either in Shimudzu FTꢀIR 8300 Spectrometer or in Perkin
Elmer FTꢀIR Spectrum RX 1 Spectrometer as neat or thin films (KBr or Nujol) as indicated in
the experimental procedures, and at room temperature. Frequencies are given in wave numbers
(cmꢀ1). Mass spectra were recorded on a Qtof Micro YA263 highꢀresolution mass spectrometer.
For column chromatography, silica gel G, 60ꢀ120 mesh was used with petroleum etherꢀethyl
acetate mixture as the eluent. For thin layer chromatography (TLC), freshly made silica gel
plates (using silica gel for TLC and petroleum ether) were used and visualization was achieved
by staining with iodine.
4.2 Extraction and isolation of friedelin (2) and cerin (3) from Quercus suberbark
2 Kg of finely powdered cork (Quercus suber) was extracted with petroleum ether in a soxhlet
apparatus for 72h. The crude yellowish solid obtained (120 g approx.), after removal of the
solvent by distillation, was dissolved in minimum volume of chloroform and chromatographed
over silica gel column (250g). Eluting the column with 2% ethyl acetate in petroleum ether
yielded pure white solid characterized as friedelin (2, 1.7g approx.) whereas ethyl acetate
produced pure white crystalline solid characterized as cerin (3, 1.1g approx., m.p. 252ꢀ256oC,
after repeated recrystallization from CHCl3).
4.3 General procedure for the BF3.OEt2 mediated reactions (towards the synthesis of the
compounds 4, 5, 6, 9 and 10):
Compound (either 2 or 7 or 8; 1mmol) was dissolved in CHCl3 (10 mL). Acetic anhydride (5
mmol)followed by BF3.OEt2(5 mmol) was added to the solution and was allowed to stir for 24h
at room temperature. 10 mL chloroform and 10 mL aqueous sodium acetate solution were added
to the reaction mixture and was allowed to reflux for 30 minutes. The reaction mixture was
cooled, extracted with chloroform (3x 25 mL), washed with saturated brine solution (2x 25 mL)
followed by water (1x 25 mL), and dried (Na2SO4). The solvent was removed by distillation to
obtain the reddish solid which after coloum chromatography furnished the products. In each case
the separated compounds were further purified by recrystallization (chloroformꢀmethanol).
4.4 Oxidation of friedel-3-enol acetate with CrO3/ CH3OOH

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Friedelꢀ3ꢀenol acetate (10, 100 mg, 0.21 mmol) was dissolved in glacial acetic acid (1 mL). CrO3
(1.5eqv.) was added to it and stirred for 2 h at room temperature. The reaction mixture was
poured into ice cold water (50 mL), filtered and washed with water repeatedly and dried
(vacuum). The residue after column chromatography produced friedelꢀ3ꢀoxoꢀ4αꢀacetate (11, 42
mg, 41%) which was further recrystallized from chloroformꢀmethanol.
4.5 Oxidation of friedel-3-enol acetate (5) and 3-chlorofriedel-3-ene (27) with mCPBA:
Friedelꢀ3ꢀenol acetate (100 mg, 0.21 mmol) was dissolved in CH2Cl2 (10 mL), and then mꢀ
CPBA (84 mg, 0.37 mmol) and NaHCO3 (aqueous, 0.5 M, 5 mL) were added (for the oxidation
of 3ꢀchlorofriedelꢀ3ꢀene: substrate 27 (40.0 mg, 0.09 mmol) + mCPBA (20 mg, 0.12 mmol) in 10
mL chloroform). The mixture was stirred for 2h at room temperature. CHCl3 (10 mL) was
poured and the organic layer was separated, washed with saturated solution of NaHCO3 (2x 15
mL), and with water (2x 15 mL), and then concentrated (vacuum) and dried (Na2SO4). Column
chromatography followed by recrystallization yielded the desired products.
4.6 General procedure for the acetylation reactions (to synthesize compounds 10, 20, 24 and
26):
10 mg of the substrate was dissolved in dry pyridine (1 mL) and acetic anhydride (1.5eqv.) was
added to it and allowed to heat at100oC for specific time (please follow the respective schemes
for the reaction times). The reaction mixture was cooled, poured into ice cold water (10 mL),
filtered and washed with cold water repeatedly and the solid was vacuum dried. The residue was
column chromatographed and further recrystallized from chloroformꢀmethanol to obtain the
corresponding pure acetyl derivative.
4.7 General procedure for the oximination reactions:
10 mg of the compound was dissolved in dry pyridine (1 mL) and hydroxylamine hydrochloride
(1.5 eqv.) was added to it and allowed to heat at1000C for 4h. The reaction mixture was cooled,
poured into ice cold water (10 mL), filtered and washed with water repeatedly and the solid was
vacuum dried. The residue was recrystallized from chloroformꢀethanol or ethanol to obtain the
corresponding pure oxime derivative.
4.8 Hydrolysis with KOH/ MeOH:
Friedelꢀ3ꢀoxoꢀ4αꢀacetate (11, 17 mg, 0.035 mmol) was dissolved in aqueous methanol (MeOH:
H2O= 9:1, 5 mL) and solid KOH (3eqv.) was added to it. The reaction mixture was refluxed for
30 minutes, cooled and then methanol was evaporated out (rota vac.). Chloroform (10 mL) was

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added to the residue, washed with water (2x 10 mL), brine (1x 10 mL) and again with water (1x
10 mL) and was dried (Na2SO4). The solvent was removed by distillation to obtain pale
yellowish solid which after column chromatography furnished the pure product friedelanꢀ3ꢀoxoꢀ
4αꢀol (21, 13 mg, 84%).
4.9 General procedure for the reduction with NaBH4:
Substrate (10 mg) was dissolved in CH2Cl2ꢀMeOH (1:1, 2 mL) and NaBH4 (1.2 equivalent) was
added. The solution was stirred for 4 hours at room temperature. Sodium hydroxide (1 M, 2 mL)
was added and the reaction mixture was extracted with CHCl3and after usual workꢀup (washed,
dried, solvent evaporated), silica gel column chromatography furnished the expected pure
products.
4.10 Procedure for the synthesis of compound 19:
Cerin (3, 100 mg) was dissolved in dry isopropanol (4 mL), and sodium (small piecedꢀcut, 20
mg) was added to it. The reaction mixture was refluxed for 2 hours and then cooled. The content
was then added drop wise to 100 mL of iceꢀcold water and the reaction mixture was extracted
with CHCl3 and after usual workꢀup (washed, dried, solvent evaporated), silica gel column
chromatography furnished compound 19 as pure white solid.
4.11 General procedure for the VilsmeierꢀHaack reaction of friedelin (2):
A solution of friedelin (2, 1 g, 2.34 mmol) in dry chloroform (25 mL) was added drop wise to a
cold and stirred solution of phosphorus oxychloride (5 mL) and dry dimethylformamide (5 mL).
The mixture was allowed to attain room temperature and then refluxed under nitrogen for 6h. It
was then concentrated under reduced pressure and poured onto ice followed by extraction with
chloroform (3 × 20 mL). The combined extracts were washed with brine (3 × 25 mL) and dried
(Na2SO4), and solvent was removed to give a yellowish solid. Purification by column
chromatography yielded the four productsꢀ 3ꢀchlorofriedelꢀ3ꢀene (27), 3ꢀchloroꢀ2ꢀformylfriedelꢀ
2ꢀene (28), 2ꢀformylꢀ3ꢀhydroxyfriedelꢀ2ꢀene (29) and 3ꢀchloroꢀ2ꢀformylꢀ4αꢀhydroxyfriedelꢀ2ꢀ
ene (30).
4.12 Procedure for the synthesis of 3-chlorofriedel-2-ene-2-carboxamide 39 from oxime 34:
In a solution of oxime 34 (20 mg, 0.04 mmol) in dry DMF (5 mL) was added anhydrous FeCl3 (5
eqv.) and the mixture was allowed to reflux for 5h. The reaction was cooled and water (15 mL)
was added. It was then extracted with diethyl ether (3 × 15 mL) and the combined organic
solvent was washed successively with water (2 × 15 mL) and brine solution (2 × 15 mL), dried

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(Na2SO4), and solvent was removed at reduced pressure to give a yellowish solid. Finally,
column chromatography furnished the 2ꢀcarboxamide friedelane derivative 37 as a pure
compound.
4.13 Allylic hydroxylation by selenium dioxide:
To a solution of 28 (or, 35, 0.1 mmol) in dioxane (10 mL) was added selenium dioxide (0.15
mmol), the mixture was heated at 1000C for 24h. The reaction mixture was then cooled and the
black selenium deposited was filtered off through Whatman 41. To the filtrate chloroform (20
mL) was poured and was washed successively with water and then with saturated brine solution,
dried over Na2SO4 and concentrated in vacuo to give a reddish gummy residue. The residue was
then column chromatographed to isolate the pure product.
4.14 General procedure for the syntheses of heterocycle-linked 2-homofriedelanes:
A mixture of compound 28 (0.1 mmol), suitable heterocycle (0.25 mmol), and K2CO3 (0.5 mmol)
in dry DMF (2 mL) was heated at 80 °C under N2 for 3 h. After cooling to room temperature, the
reaction mixture was poured onto iceꢀcold water (30 mL), and was extracted with chloroform (3
× 15 mL) and the combined organic solvent was washed successively with water (2 × 25 mL)
and brine solution (2 × 25 mL), dried (Na2SO4), and solvent was removed at reduced pressure to
give a yellowish solid. Finally, column chromatography furnished the heterocycleꢀlinked 2ꢀ
homofriedelane derivatives.
4.15 Characterization of the products
4.15.1 Friedelin (2): Eluent in column chromatography: 2% ethyl acetate in petroleum ether.
o
o
1
White crystalline solid, m.p. 262ꢀ263 C (pet. etherꢀ ethyl acetate, lit.26a 262ꢀ263 C). H NMR
(300 MHz, CDCl3): δ 0.73 (s, 3H, Meꢀ24), 0.87 (s, 3H, Meꢀ25), 0.89 (s, 3H, Meꢀ23), 0.95(s, 3H,
Meꢀ30), 1.00 (s, 6H, Meꢀ26 and Meꢀ29), 1.05 (s, 3H, Meꢀ27), 1.18(s, 3H, Meꢀ28), 1.91ꢀ 2.02 (m,
1H, Hꢀ1), 2.20ꢀ2.47 (m, 3H, Hꢀ2 and Hꢀ4). 13C NMR (75 MHz, CDCl3): δ 6.80 (Cꢀ23), 14.61 (Cꢀ
24), 17.91 (Cꢀ25), 18.18 (Cꢀ7), 18.64 (Cꢀ27), 20.22 (Cꢀ26), 22.24 (Cꢀ1), 28.12 (Cꢀ20), 29.93 (Cꢀ
17), 30.45 (Cꢀ12), 31.74 (Cꢀ29), 32.04 (Cꢀ28), 32.35 (Cꢀ21), 32.69 (Cꢀ15), 34.99 (Cꢀ30), 35.28
(Cꢀ19), 35.55 (Cꢀ11), 35.94 (Cꢀ16), 37.37 (Cꢀ9), 38.23 (Cꢀ14), 39.20 (Cꢀ22), 39.63 (Cꢀ13), 41.21
(Cꢀ6), 41.49 (Cꢀ2), 42.11 (Cꢀ5), 42.70 (Cꢀ18), 53.03 (Cꢀ8), 58.15 (Cꢀ4), 59.38 (Cꢀ10), 213.37 (Cꢀ
3). FTIR (nujol, cmꢀ1): ν 1714, 1380, 1302, 1257, 1103, 1071, 1046, 1004, 795, 719.

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4.15.2 Cerin (3): Eluent in column chromatography: ethyl acetate. White crystalline solid, m.p.
o
o
231 C (ethyl acetate, lit.4l 230 C).1H NMR (300 MHz, CDCl3): δ 0.73 (s, 3H, Meꢀ24), 0.87 (s,
3H, Meꢀ25), 0.89 (d, J=6.0 Hz, 3H, Meꢀ23), 0.95 (s, 3H, Meꢀ30), 1.01 (s, 6H, Meꢀ27 and Meꢀ
28), 1.05 (s, 3H, Meꢀ26), 1.18 (s, 3H, Meꢀ29), 1.57 (d, J= 4.8Hz), 2.18 (d, J= 5.1Hz, 1H, OH ),
3.60 (m, 1H, Hꢀ3α), 3.89 (m, 1Η, 2β).
4.15.3 Friedel-2-ene (4): Eluent in column chromatography: petroleum ether. Yield: 7ꢀ16%,
o
o
white prism like crystals, m.p. 246 C (chloroformꢀmethanol, lit.15a 246ꢀ248 C).1H NMR (300
MHz, CDCl3): δ 0.75 (s, 3H, Meꢀ24), 0.80 (s, 3H, Meꢀ25), 0.86 (s, 3H, Meꢀ23), 0.94 (s, 3H, Meꢀ
30), 1.03 (s, 3H, Meꢀ26 and Meꢀ29), 1.09 (s, 3H, Meꢀ27), 1.15 (s, 3H, Meꢀ28), 2.27 (d, J=13.8
Hz, 2H, Hꢀ1), 2.65 (d, J=10.5 Hz, 1H, Hꢀ4), 4.86 (s, 1H, Hꢀ2), 5.13ꢀ5.21 (m, 1H, Hꢀ3).13C NMR
(75 MHz, CDCl3): δ 16.36, 17.80, 18.72, 18.79, 21.43, 21.69 (2), 23.83, 24.14, 25.17, 26.55,
32.38, 33.27, 33.34, 33.47, 34.61, 34.87, 35.53, 36.74, 37.66, 38.71, 39.47, 40.51, 41.29, 42.14,
44.77, 50.87, 56.50, 133.02 (Cꢀ2), 134.67 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 1376, 1363, 1343, 1257,
1166, 1142, 1085, 1036, 967, 820, 803, 720.
4.15.4 Friedel-3-enol-acetate (5): Eluent in column chromatography: 2% ethyl acetate in
o
1
petroleum ether. Yield: 8ꢀ60%, white crystalline solid, m.p. 262 C (chloroformꢀmethanol). H
NMR (300 MHz, CDCl3): δ 0.85 (s, 3H, Meꢀ25), 0.95 (s, 3H, Meꢀ30), 1.00 (s, 6H, Meꢀ26 and
Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.02 (s, 3H, Meꢀ24), 1.18 (s, 3H, 28ꢀMe), 1.59 (s, 3H, Meꢀ23),
2.12 (s, 3H, ꢀCH3 of ꢀOAc). 13C NMR (75 MHz, CDCl3): δ 9.55, 17.46, 18.16, 18.26, 18.67,
20.10, 20.69, 20.88, 28.20, 28.39, 30.07, 30.61, 31.83, 32.16, 32.39, 32.90, 35.04, 35.25, 35.42,
36.11, 37.08, 38.22, 38.39, 38.66, 39.31, 39.84, 42.95, 52.75, 56.10, 130.57 (Cꢀ4), 141.31 (Cꢀ3),
168.98 (>C=O of ꢀOAc). FTIR (nujol, cmꢀ1): ν 667, 759, 1070, 1222, 1382, 1456, 1749 (>C=O
of ꢀOAc), 2337. LRESIMS m/z (%): 491.3 (33) [M+ Na]+, 489.3 (100). Analysis calcd: C, 81.99;
H, 11. 18. Found: C, 81.56; H, 10.89.
4.15.5 Friedel-2-oxo-3-enol acetate (6): Eluent in column chromatography: 5% ethyl acetate in
o
petroleum ether. Yield: 22ꢀ32%, yellowishꢀwhite solid, m.p. 280ꢀ282 C (chloroformꢀmethanol,
o
1
lit.26b 283ꢀ285 C). H NMR (300 MHz, CDCl3): δ 0.93 (s, 3H, Meꢀ25), 0.95 (s, 3H, Meꢀ30),
0.99 (s, 6H, Meꢀ26 and Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.16 (s, 3H, Meꢀ24), 1.18 (s, 3H, Meꢀ28),
13
1.76 (s, 3H, Meꢀ23), 2.24 (s, 3H, CH3 of ꢀOAc). C NMR (75 MHz, CDCl3): δ 11.46, 17.64,
17.95, 18.59, 19.11, 20.13, 20.37, 28.14, 29.99, 30.21, 31.76, 32.10, 32.19, 32.73, 34.04, 34.52,
35.01, 35.31, 35.88, 36.89, 37.83, 38.23, 39.22, 39.72, 40.54, 42.74, 52.41, 54.55, 140.87 (Cꢀ4),

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157.02 (Cꢀ3), 168.58 (ꢀCH3 of ꢀOAc), 191.89 (Cꢀ2). FTIR (neat, cmꢀ1): ν 752, 916, 1006, 1089,
1219, 1325, 1383, 1462, 1523, 1682, 1761, 2862, 2929. LRESIMS m/z (%): 483.25 (32)
[M+H]+, 465.26 (65), 413.16 (47), 315.09 (51), 301.08 (100). Analysis calcd: C, 79.62; H, 10.44.
Found: C, 79.78; H, 10.52.
o
4.15.6 Friedelane-3-hydroxyimino (7): Yellowishꢀwhite solid, m.p. 283ꢀ284 C (chloroformꢀ
o
1
methanol, lit.1a 280ꢀ282 C). H NMR (300 MHz, CDCl3): δ 0.67 (s, 3H, Meꢀ25), 0.77 (s, 3H,
Meꢀ30), 0.88 (s, 3H, Meꢀ26), 0.89 (s, 3H, Meꢀ29),0.93 (s, 6H, Meꢀ23 and Meꢀ24), 0.98 (s, 3H,
Meꢀ27), 1.10 (s, 3H, Meꢀ28), 1.70 (m, 1H, Hꢀ2eq), 1.97 (m, 1H), 2.11 (s, 1H, Hꢀ4), 3.36 (d,
13
J=12Hz, Hꢀ2ax). C NMR (75 MHz, CDCl3): δ 7.34, 13.20, 16.94, 17.32, 17.65, 19.22, 19.55,
23.47, 27.15, 28.68, 28.99, 29.52, 30.76, 31.08, 31.38, 31.78, 34.01, 34.31, 34.55, 35.04, 36.30,
37.27, 38.24, 38.64, 40.12, 41.76, 49.92, 52.07, 58.96, 159.61.
4.15.7 Friedelan-3β−ol (8): Eluent in column chromatography: 5% ethyl acetate in petroleum
o
ether. Yield: 72%, white crystalline solid, m. p. 290 C (pet. etherꢀ ethyl acetate, lit.26c 290ꢀ291
oC). 1H NMR (300 MHz, CDCl3): δ 0.86(s, 3H, Meꢀ25), 0.93 (s, 3H, Meꢀ24), 0.95 (d, J=1.2 Hz,
3H, Meꢀ23), 0.96 (s, 3H, Meꢀ30), 0.99 (s, 6H, Meꢀ26 and Meꢀ29), 1.00 (s, 3H, Meꢀ27), 1.17 (s,
3H, Meꢀ28), 1.75 (dt, J=12.8 and 3.2 Hz, 1H, Hꢀ6,), 3.75 (m, 1H, Hꢀ3). 13C NMR (75 MHz,
CDCl3): δ 11.63 (Cꢀ23), 15.76 (Cꢀ1), 16.39 (Cꢀ24), 17.52 (Cꢀ7), 18.24 (Cꢀ25), 18.66 (Cꢀ26),
20.12 (Cꢀ27), 28.17 (Cꢀ20), 30.00 (Cꢀ17), 30.62 (Cꢀ15), 31.78 (Cꢀ29), 32.07 (Cꢀ28), 32.29 (Cꢀ
21), 32.76 (Cꢀ12), 35.03 (Cꢀ30), 35.13 (Cꢀ2), 35.31 (Cꢀ19), 35.52 (Cꢀ11), 36.04 (Cꢀ16), 37.06,
37.79 (Cꢀ9), 38.33 (Cꢀ13), 39.26 (Cꢀ22), 39.64 (Cꢀ14), 41.67 (Cꢀ5), 42.76 (Cꢀ6), 49.12 (Cꢀ4),
53.16 (Cꢀ8), 61.29 (Cꢀ10), 72.75 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 3474, 1381, 1174, 1044, 999, 943,
916, 719.
4.15.8 Lactam 9: Eluent in column chromatography: 35% ethyl acetate in petroleum ether.
0
0
1
Yield: 67%, yellow amorphous solid, m.p. 266ꢀ267 C (lit1a 266ꢀ268 C). H NMR (300 MHz,
CDCl3): δ 0.81 (s, 3H, Meꢀ24), 0.81 (s, 3H, Meꢀ25), 0.95 (s, 3H, Meꢀ30), 0.98 (s, 3H, Meꢀ27),
0.99 (s, 3H, Meꢀ29), 1.00 (s, 3H, Meꢀ26), 1.04 (d, J=6.6Hz, 3H, Meꢀ23), 1.17 (s, 3H, Meꢀ28),
13
1.73 (brs, 1H, Hꢀ10), 2.38 (m, 2H, Hꢀ2), 3.26 (q, J=6.6 Hz, 1H, Hꢀ4), 5.28 (brs, 1H, NꢀH). C
NMR (75 MHz, CDCl3): δ 13.88 (Cꢀ 24), 16.03 (Cꢀ23), 17.95 (Cꢀ25), 18.35 (Cꢀ1), 18.44 (Cꢀ7),
18.58 (Cꢀ26), 20.21 (Cꢀ27), 28.17 (Cꢀ20), 29.99 (Cꢀ17), 30.66 (Cꢀ12), 31.75 (Cꢀ29), 32.04 (Cꢀ
15), 32.40 (Cꢀ28), 32.76 (Cꢀ21), 35.03 (Cꢀ30), 35.29 (Cꢀ11), 35.50 (Cꢀ19), 36.01 (Cꢀ16), 36.52
(Cꢀ2), 38.43 (Cꢀ9), 38.51 (Cꢀ14), 39.24 (Cꢀ22), 39.27 (Cꢀ5 and Cꢀ6), 39.86 (Cꢀ13), 42.72 (Cꢀ18),

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52.77 (Cꢀ8), 59.02 (Cꢀ4), 65.24 (Cꢀ10), 177.07 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 2928, 2867, 1672
(C=O), 1458 (NꢀH), 1362 (CꢀN), 734 (NꢀH).
4.15.9 Friedelane-3β-acetate (10): Eluent in column chromatography: 1% ethyl acetate in
o
petroleum ether. Yield: 30%, white crystalline solid, m. p. 298 C (chloroformꢀmethanol, lit.26c
o
1
299 C). H NMR (300 MHz, CDCl3): δ 0.75 (s, 3H, Meꢀ24), 0.77 (s, 3H, Meꢀ25), 0.82 (s, 3H,
Meꢀ23), 0.95 (s, 3H, Meꢀ30), 0.99 (s, 6H, Meꢀ26, Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.17 (s, 3H, Meꢀ
28), 1.78 (dt, J=12.8 and 3.2 Hz, 1H, Hꢀ6), 2.01 (s, 3H, ꢀOCOCH3), 2.03ꢀ 2.12 (m, 3H, Hꢀ2 and
Hꢀ4), 4.62 (m, 1H, Hꢀ3). 13C NMR (75 MHz, CDCl3): δ 9.93 (Cꢀ23), 14.50 (Cꢀ24), 17.85 (Cꢀ25),
18.12 (Cꢀ7), 18.65 (Cꢀ27), 19.33 (ꢀCH3 of ꢀOAc), 20.16 (Cꢀ26), 21.36 (Cꢀ1), 28.18 (Cꢀ20), 30.01
(Cꢀ17), 30.57 (Cꢀ12), 31.80 (Cꢀ29), 32.10 (Cꢀ28), 32.35 (Cꢀ15), 32.71 (Cꢀ2), 32.80 (Cꢀ21), 35.02
(Cꢀ30), 35.32 (Cꢀ19), 35.53 (Cꢀ11), 36.05 (Cꢀ16), 37.00 (Cꢀ9), 38.30 (Cꢀ14), 38.39 (Cꢀ5), 39.27
(Cꢀ22), 39.68 (Cꢀ13), 41.33 (Cꢀ6), 42.81 (Cꢀ18), 50.03 (Cꢀ4), 52.98 (Cꢀ8), 59.89 (Cꢀ10), 75.19
(Cꢀ3), 170.99 (>C=O of ꢀOAc). FTIR (nujol, cmꢀ1): ν 1736, 1379, 1049, 1019, 972, 754, 721.
Analysis calcd: C, 81.64; H, 11.56. Found: C, 81.55; H, 11.43.
4.15.10 Friedel-3-oxo-4α-acetate (11): Eluent in column chromatography: 2% ethyl acetate in
petroleum ether. Yield: 12ꢀ41%, white crystalline solid, m.p. 174ꢀ176 oC (chloroformꢀmethanol).
1H NMR (300 MHz, CDCl3): δ 0.80 (s, 3H, Meꢀ25), 0.86 (s, 3H, Meꢀ24), 0.96 (s, 3H, Meꢀ30),
1.00 (s, 6H, Meꢀ26 and Meꢀ29), 1.07 (s, 3H, Meꢀ27),1.18 (s, 3H, Meꢀ28),1.30 (s, 3H, Meꢀ23),
1.93ꢀ 2.02 (m, 1H, Hꢀ1), 2.26ꢀ2.52 (m, 2H, Hꢀ2), 2.14 (ꢀCH3 of ꢀOAc).13C NMR (75 MHz,
CDCl3): δ 12.64, 15.68, 17.95, 18.13, 18.73, 20.19, 21.50, 22.98, 28.20, 30.03, 30.55, 31.84,
32.12, 32.38, 32.85, 34.29, 35.00, 35.34, 35.95, 36.05, 37.29, 38.03, 38.32, 39.28, 39.70, 42.88,
46.05, 50.34, 52.47, 89.09 (Cꢀ4), 170.11 (ꢀCH3 of ꢀOAc), 208.30 (Cꢀ3). FTIR (nujol, cmꢀ1): ν
722, 1119, 1245, 1377, 1508, 1736, 2345. LRESIMS m/z (%): 507.5 (100) [M+ Na]+, 508.5
(46). Analysis calcd: C, 79.29; H, 10.81. Found: C, 79.38; H, 10.73.
4.15.11 Friedel-3-oxo-4β-acetate (12): Eluent in column chromatography: 5% ethyl acetate in
o
petroleum ether Yield: 35%, white crystalline solid, m.p. 228ꢀ230 C (chloroformꢀmethanol). 1H
NMR (300 MHz, CDCl3): δ 0.88 (s, 3H, Meꢀ25), 0.91 (s, 3H, Meꢀ24), 0.96 (s, 3H, Meꢀ30), 1.00
(s, 3H, Meꢀ26), 1.01 (s, 3H, Meꢀ29), 1.05 (s, 3H, Meꢀ27), 1.18 (s, 3H, Meꢀ28), 1.84 (s, 3H, Meꢀ
23), 2.08 (ꢀCH3 of ꢀOAc), 2.29ꢀ2.40 (m, 1H, Hαꢀ2), 2.51ꢀ2.59 (m, 1H, Hβꢀ2). 13C NMR (75
MHz, CDCl3): δ 15.02, 17.64, 17.99, 18.73, 19.18, 20.33, 21.71, 22.84, 28.18, 30.02, 30.49,
31.76, 32.12, 32.49, 32.80, 33.22, 35.05, 35.39, 36.02, 36.08, 37.40, 37.45, 38.34, 39.29, 39.73,

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42.85, 47.00, 51.98, 53.23, 89.83 (Cꢀ4), 169.69 (ꢀCH3 of ꢀOAc), 205.79 (Cꢀ3). FTIR (nujol, cmꢀ
1): ν 1755, 1723, 1462, 1377, 1235, 1192, 1118, 1090, 1017, 605, 500. Analysis calcd: C, 79.29;
H, 10.81. Found: C, 79.41; H, 10.65.
4.15.12 Friedel-3β-ol-4α-acetate (13): Eluent in column chromatography: 2% ethyl acetate in
petroleum ether. Yield: 27%, pale yellow solid, m.p. 230 oC.1H NMR (300 MHz, CDCl3): δ 0.83
(s, 3H, Meꢀ25), 0.94 (s, 3H, Meꢀ30), 0.99 (s, 6H, Meꢀ26 and Meꢀ29), 1.14 (d, J= 1.2 Hz, 3H,
Meꢀ27), 1.15 (s, 3H, Meꢀ24), 1.16 (s, 3H, Meꢀ28), 1.20 (d, J=1.5 Hz, 3H, Meꢀ23), 1.75ꢀ1.78 (m,
1H, Hꢀ10), 2.07 (q, J=1.5 Hz, ꢀCH3 of ꢀOAc), 2.15 (t, J=3.9 Hz, Hꢀ3). 13C NMR (75 MHz,
CDCl3): δ 12.18 (Cꢀ23), 15.25 (Cꢀ24), 17.70 (Cꢀ25), 17.82 (Cꢀ1), 18.04 (Cꢀ7), 18.71 (Cꢀ27),
20.17 (Cꢀ26), 21.02 (CH3 of ꢀOAc), 27.86 (Cꢀ6), 28.15 (Cꢀ20), 30.00 (Cꢀ17), 30.49 (Cꢀ12),
31.76 (Cꢀ29), 32.10 (Cꢀ28), 32.33 (Cꢀ15), 32.77 (Cꢀ21), 35.05 (Cꢀ30), 35.34(Cꢀ11),35.52 (Cꢀ16),
36.00 (Cꢀ22), 36.46 (Cꢀ19), 36.66 (Cꢀ9), 38.27 (Cꢀ14), 38.36 (Cꢀ5), 39.25 (Cꢀ2), 39.70 (Cꢀ13),
42.78 (Cꢀ18), 48.10 (Cꢀ8), 52.36 (Cꢀ10), 71.65 (Cꢀ3), 88.05 (Cꢀ4), 169.51 (>C=O of ꢀOAc).
FTIR (nujol, cmꢀ1): ν 615,722, 838, 1041, 1148, 1213, 1241, 1377, 1560, 1654, 1742. Analysis
calcd: C, 78.96; H, 11.18. Found: C, 78.83; H, 10.97.
4.15.13 Friedelin-2,3-lactone (14): Eluent in column chromatography: 5% ethyl acetate in
o
o
petroleum ether. Yield: 81%, white crystalline solid, m.p. 287ꢀ289 C (lit.1a 288ꢀ290 C).1H
NMR (300 MHz, CDCl3): δ 0.85 (s, 3H, Meꢀ25), 0.89 (s, 3H, Meꢀ24), 0.91 (s, 3H, Meꢀ26), 0.96
(s, 6H, Meꢀ27 and Meꢀ30), 1.01 (s, 3H, Meꢀ 29), 1.15 (s, 3H, Meꢀ28), 1.23 (d, 3H, J = 6.3 Hz,
Meꢀ23), 1.95 (m, 1H, Hꢀ1ax), 2.55 (td, 1H, J= 1.5, 13.0 and 13.0 Hz, Hꢀ2ax), 2.65 (ddd, 1H, J =
1.5, 7.0 and 13.0 Hz, Hꢀ2eq), 4.24 (q, 1H, J = 6.3 Hz, Hꢀ4). 13C NMR (75 MHz, CDCl3): δ 13.45
(Cꢀ23), 16.22 (Cꢀ24), 17.90 (Cꢀ25), 18.03 (Cꢀ7), 18.55 (Cꢀ1), 18.58 (Cꢀ26), 20.20 (Cꢀ27), 28.17
(Cꢀ20), 29.99 (Cꢀ17), 30.61 (Cꢀ12), 31.76 (Cꢀ29), 32.06 (Cꢀ28), 32.37 (Cꢀ15), 32.75 (Cꢀ21),
34.36 (Cꢀ2), 35.03 (Cꢀ30), 35.31 (Cꢀ11), 35.42 (Cꢀ16), 35.97 (Cꢀ19), 38.20 (Cꢀ9), 38.39 (Cꢀ14),
38.47 (Cꢀ6), 39.23 (Cꢀ22), 39.35 (Cꢀ13), 40.79 (Cꢀ5), 42.73 (Cꢀ18), 52.73 (Cꢀ8), 63.99 (Cꢀ 10),
84.92(Cꢀ4), 175.59 (C3). FTIR: (KBr, cmꢀ1): ν 2945, 1734 (C=O), 1072 (CO), 752.
4.15.14 3,4-Seco-friedelane-3,4-diol (15): Eluent in column chromatography: 35% ethyl acetate
o
in petroleum ether. Yield 72%, white powdered solid, m.p. 249 C.1H NMR (300 MHz, CDCl3):
δ 0.88 (s, 3H, Meꢀ24), 0.93 (s, 3H, Meꢀ25), 0.95 (s, 3H, Meꢀ30), 0.98 (s, 3H, Meꢀ23), 1.00 (s,
6H, Meꢀ26 and Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.18 (s, 3H, Meꢀ28), 3.51ꢀ3.65 (m, 3H, Hꢀ3 and Hꢀ
4). 13C NMR (75 MHz, CDCl3): δ 16.37 (Cꢀ23), 17.81 (Cꢀ24), 18.02, 18.65 (Cꢀ27), 18.79(Cꢀ25),

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20.16 (Cꢀ26), 21.98, 28.16, 30.00, 30.23, 31.85 (Cꢀ29), 32.10 (Cꢀ28), 32.26, 32.82, 34.94 (Cꢀ30),
35.07, 35.29, 36.06, 38.30, 39.28, 39.56, 41.91, 42.81, 52.84, 58.53, 63.25 (Cꢀ3), 75.87 (Cꢀ4).
FTIR (neat, cmꢀ1): ν 3392, 2937, 2868, 1652, 1458, 1388, 1068. Analysis calcd: C, 80.65; H,
12.18. Found: C, 80.20, H, 12.01.
4.15.15 Friedelane-3-oximino-4α−ol (16): Yield: 88%, pale yellow solid, m.p. 227 oC.1H NMR
(300 MHz, DMSOꢀd6): δ 0.73 (s, 3H, Meꢀ24), 0.81 (s, 3H, Meꢀ25), 0.96 (s, 3H, Meꢀ30), 0.99 (s,
6H, Meꢀ26 and Meꢀ29), 1.12 (s, 3H, Meꢀ27), 1.17 (s, 3H, Meꢀ28), 1.26 (s, 3H, Meꢀ23), 1.70ꢀ2.01
(m, 3H, Hꢀ2 and Hꢀ10), 4.39 (br s, 1H, ꢀOH), 10.38 (br s, 1H, ꢀNOH). 13C NMR (75 MHz,
DMSOꢀd6): δ 17.16, 18.12, 18.67, 18.93, 19.85, 20.36, 28.32, 30.06, 30.59, 32.16, 32.35, 32.99,
33.75, 35.24, 35.80, 36.11, 36.97, 38.25, 39.50, 39.77, 40.05, 40.33, 40.61, 40.89, 42.90, 43.47,
49.44, 52.37, 76.62 (Cꢀ4), 161.14 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 3442, 3301, 2723, 1378, 1302,
1178, 1045, 992, 944, 919, 769, 725, 572.
4.15.16 Friedelan-3β-amine-4α-ol (17): Yield: 63%, pale yellow smallꢀflowerꢀlike crystals,
o
m.p. 242 C (chloroformꢀethanol).1H NMR (300 MHz, CDCl3): δ 0.84 (s, 3H, Meꢀ24), 0.88 (s,
3H, Meꢀ25), 0.93 (s, 3H, Meꢀ30), 0.95 (s, 6H, Meꢀ29), 1.10 (s, 3H, Meꢀ27), 1.14 (s, 3H, Meꢀ26),
1.18 (s, 3H, Meꢀ28), 2.08 (m, 3H, Meꢀ23), 2.17ꢀ 2.28 (m, 1H, Hꢀ10), 2.47ꢀ 2.56 (m, 1H, Hꢀ2),
13
3.61ꢀ 3.83 (br hump, ꢀOH), 5.01ꢀ 5.29 (br hump, ꢀNH2). C NMR (75 MHz, CDCl3): δ 16.44
(CH3ꢀ24), 16.81 (CH3ꢀ25), 16.94 (CH3ꢀ23), 17.66 (CH3ꢀ27), 19.15 (CH3ꢀ26), 23.78, 24.78,
27.14, 28.68, 28.96, 29.02, 30.80, 31.11, 31.32, 31.79 (CH3ꢀ29), 33.94 (CH3ꢀ28), 34.29, 34.36,
34.93 (CH3ꢀ30), 37.27, 37.33, 38.23, 38.62, 41.81, 51.36, 52.26, 52.94, 54.8 (Cꢀ3), 76.20 (Cꢀ4).
Analysis calcd: C, 81.20; H, 12.04; N, 3.16 Found: C, 81.40; H, 11.95; N, 3.09.
4.15.17 Friedelane-2α,3β-diol (18): Eluent in column chromatography: 50% ethyl acetate in
o
petroleum ether. Yield: 68%, white crystalline solid, m.p. 288ꢀ290 C (ethyl acetate, lit15a 287ꢀ
o
1
290 C). H NMR (300 MHz, CDCl3): δ 0.85 (s, 3H, Meꢀ24), 0.88 (s, 3H, Meꢀ25), 0.93 (s, 3H,
Meꢀ23), 0.95 (s, 3H, Meꢀ30), 0.99 (s, 3H, Meꢀ26), 1.01 (s, 3H, Meꢀ29), 1.07 (s, 3H, Meꢀ27),
1.17 (s, 3H, Meꢀ28), 3.55 (s, 1H, Hꢀ2), 3.99 (d, J=2.7 Hz, 1H, Hꢀ3). 13C NMR (75 MHz, CDCl3):
δ 10.90, 15.93, 17.54, 18.17, 18.74, 20.15, 23.96, 28.19, 30.05, 30.63, 31.80, 32.14, 32.36, 32.84,
35.05, 35.37, 35.52, 36.09, 36.55, 37.82, 38.42, 39.30, 39.73, 41.41, 42.87, 43.71, 52.31, 53.27,
71.43 (Cꢀ2), 77.22 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 3443, 3300, 2724, 1377, 1301, 1179, 1045, 992,
943, 918, 768, 724, 572. Analysis calcd: C, 81.02; H, 11.79. Found: C, 81.32; H, 11.35.

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4.15.18 3-Epipachysandiol A (19): Eluent in column chromatography: 50% ethyl acetate in
o
petroleum ether. Yield: 62%, white needleꢀshaped crystals, m.p. 282ꢀ283 C (ethyl acetate, lit.15a
o
1
281ꢀ 283 C). H NMR (300 MHz, CDCl3): δ 0.80 (d, J= 6.3 Hz, 3H, CH3ꢀ24), 0.90 (d, J= 6.6
Hz, 3H, CH3ꢀ25), 0.95 (s, 1H, CH3ꢀ30), 0.99 (s, 6H, CH3ꢀ26 and CH3ꢀ29), 1.00 (s, 1H, CH3ꢀ 2),
1.17 (s, 1H, CH3ꢀ28), 1.26 (s, 1H, CH3ꢀ23), 3.18 (dd, J= 9 Hz and 10.5 Hz, Cꢀ3), 3.38ꢀ 3.47 (m,
13
1H, Cꢀ2). C NMR (75 MHz, CDCl3): δ 9.71, 14.76, 17.77, 18.15, 18.60, 20.13, 27.91, 28.15,
29.34, 30.00, 30.55, 31.76, 32.09, 32.37, 32.81, 35.00, 35.35, 35.53, 36.04, 36.96, 38.26, 38.32,
39.26, 39.70, 41.17, 42.83, 49.78, 53.12, 57.41, 77.19, 77.50. FTIR (KBr, cmꢀ1): ν 3416, 2934,
2866, 1702, 1635, 1461, 1386, 1034, 592. LRESIMS m/z (%): 467.5 (100) [M + Na]+, 468.5
(42).Analysis calcd: C, 81.02; H, 11.79. Found: C, 81.40, H, 11.92.
4.15.19 Friedelane-3β,4α-diacetate (20): Eluent in column chromatography: petroleum ether.
o
Yield: 95%, white solid, m.p. 209ꢀ210 C.1H NMR (300 MHz, CDCl3): δ 0.88 (s, 3H, Meꢀ24),
0.91 (s, 3H, Meꢀ25), 0.95 (s, 3H, Meꢀ30), 1.00 (s, 6H, Meꢀ26 and Meꢀ29), 1.06 (d, J=1.8 Hz, 3H,
Meꢀ27), 1.18 (s, 3H, Meꢀ28), 1.26 (s, 3H, Meꢀ23), 2.07 (s, 3H, ꢀCH3 of ꢀOAc), 2.08 (s, 3H, ꢀCH3
of ꢀOAc), 2.90ꢀ3.06 (m, 1H, Hꢀ3). FTIR (nujol, cmꢀ1): ν 1749, 1734, 1717, 1459, 1375, 1233,
1112, 1014, 955, 800, 719, 599.
4.15.20 Friedelan-3-oxo-4α-ol (21): Eluent in column chromatography: 10% ethyl acetate in
o
o
1
petroleum ether. Yield: 84%, needle shaped crystals, m.p. 268ꢀ270 C (lit.15e 269ꢀ271 C). H
NMR (300 MHz, CDCl3): δ 0.81 (s, 3H, Meꢀ25), 086 (s, 3H, Meꢀ24),0.95 (s, 3H, Meꢀ30), 0.99
(s, 6H, Meꢀ26 and Meꢀ29), 1.06 (d, J=3.9 Hz, 3H, Meꢀ27), 1.16 (s, 3H, Meꢀ23), 1.17 (s, 3H, Meꢀ
28), 2.11 (d, J=12.6 Hz, 1H, Hꢀ10), 2.22 (d, J= 14.1 Hz, 1H, Hꢀ2), 2.95 (m, 1H, Hꢀ2). 13C NMR
(75 MHz, CDCl3): δ 16.74 (Meꢀ23), 16.91 (Meꢀ24),17.86 (Cꢀ1), 18.02 (Meꢀ25), 18.77 (Meꢀ27),
20.29 (Meꢀ26), 21.72 (Cꢀ7), 28.21 (Cꢀ20), 30.06 (Cꢀ17), 30.57 (Cꢀ12), 31.79 (Meꢀ29), 32.13
(Meꢀ28), 32.51(Cꢀ15), 32.86 (Cꢀ21), 33.50 (Cꢀ19), 35.05 (Meꢀ30), 35.42 (Cꢀ11), 35.83 (Cꢀ16),
36.09 (Cꢀ22), 37.08 (Cꢀ6), 37.25 (Cꢀ9), 38.33 (Cꢀ14), 39.31 (Cꢀ2), 39.77 (Cꢀ13), 42.89 (Cꢀ18),
44.63 (Cꢀ5), 49.38 (Cꢀ8), 52.45 (Cꢀ10), 81.08 (Cꢀ4), 212.92 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 3447,
1702, 1377, 1108, 1068, 746, 722. Analysis calcd: C, 81.39; H, 11.38. Found: C, 88.45; H,
11.43.
4.15.21 Friedelane-3β,4α-diol (22): Eluent in column chromatography: 20% ethyl acetate in
o
1
petroleum ether. Yield: 62%, m.p. 241ꢀ242 C (lit15e 240ꢀ241oC). H NMR (300 MHz, CDCl3):
δ 0.84 (s, 3H, Meꢀ25), 0.87 (s, 3H, Meꢀ29),0.94 (s, 3H, Meꢀ26), 0.99 (s, 3H, Meꢀ30), 1.05 (s, 3H,

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Meꢀ27),1.17 (s, 3H, Meꢀ28),1.26 (d, J= 13.2 Hz, 6H, Meꢀ23& Meꢀ24), 1.77 (m, 1H, Hꢀ2eq), 2.07
(s, 1H, OH), 2.18 (s, 1H, OH), 3.57 (br s, 1H, Hꢀ2ax) 4.74 (s, 1H, Hꢀ4). 13C NMR (75 MHz,
CDCl3): δ12.19, 15.28, 17.73, 17.84, 18.70, 18.76, 20.18, 27.88, 28.18, 30.04, 30.52, 31.78,
32.12, 32.39, 32.84, 35.05, 35.39, 35.56, 36.06, 36.50, 36.72, 38.31, 38.40, 39.29, 39.75, 42.86,
48.16, 52.41, 81.04 (Cꢀ3), 88.09 (Cꢀ4). FTIR (nujol, cmꢀ1): ν 3443, 3300, 2724, 1377, 1301,
1179, 1045, 992, 943, 918, 768, 724, 572. Analysis calcd: C, 81.02; H, 11.79. Found: C, 81.32;
H, 11.35.
4.15.22 Cyclic amine 23: Eluent in column chromatography: methanol. Yield: 63%, white
crystalline solid, m.p. 228 oC (aqueous ethanol). 1H NMR (300 MHz, CDCl3): δ 0.84 (s, 3H, Meꢀ
24), 0.87 (s, 3H, Meꢀ25), 0.92 (d, J= 3 Hz, 3H, Meꢀ23), 0.94 (s, 3H, Meꢀ30), 0.97 (s, 3H, Meꢀ
27), 0.99 (s, 3H, Meꢀ26), 1.00 (s, 3H, Meꢀ29), 1.17 (s, 3H, Meꢀ28),1.79ꢀ1.86 (m, 1H, Hβꢀ3), 2.13
(dd, J=12 Hz, 6 Hz; 1H, Hꢀ4), 2.71ꢀ2.81 (m, 1H, Hαꢀ3), 3.07ꢀ3.14 (m, 1H, NH). 13C NMR (75
MHz, CDCl3): δ 14.94 (Cꢀ24), 17.55 (Cꢀ23), 17.76 (Cꢀ25), 18.30 (Cꢀ7), 18.69 (Cꢀ27), 20.22 (Cꢀ
26), 21.08 (Cꢀ1), 28.18 (Cꢀ20), 28.99 (Cꢀ2), 30.04 (Cꢀ17), 30.57 (Cꢀ12), 31.81 (Cꢀ29), 32.09 (Cꢀ
28), 32.43 (Cꢀ15), 32.87 (Cꢀ21), 34.88 (Cꢀ11), 35.01 (Cꢀ30), 35.33 (Cꢀ19), 36.16 (Cꢀ16), 38.38
(Cꢀ14), 38.73 (Cꢀ9), 39.28 (Cꢀ22), 39.46 (Cꢀ13), 40.24 (Cꢀ6), 41.67 (Cꢀ5), 42.85 (Cꢀ18), 47.94
(Cꢀ3), 52.78 (Cꢀ8), 60.28 (Cꢀ10), 70.52 (Cꢀ4). FTIR (nujol, cmꢀ1): ν 669, 786, 1145 (br., CꢀN
str.), 1384, 1510, 1558, 1651 (NꢀH, def.), 2337, 2362, 3340, 3423 (NꢀH, str.). Analysis calcd: C,
84.24; H, 12.49. Found: C, 83.93; H, 12.25.
4.15.23 Friedelan-3-oxo-2α−acetate (24): Eluent in column chromatography: 2% ethyl acetate
o
o
1
in petroleum ether. Yield: 78%, white solid, m.p. 268ꢀ269 C (lit.15a 269.5ꢀ271 C). H NMR
(300 MHz, CDCl3): δ 0.71 (s, 3H, Meꢀ24), 0.84 (s, 3H, Meꢀ25), 0.89 (d, J= 6.6 Hz, 3H, Meꢀ23),
0.96 (s, 3H, Meꢀ30), 1.00 (s, 6H, Meꢀ26 and Meꢀ29), 1.07 (s, 3H, Meꢀ27), 1.18 (s, 3H, Meꢀ28),
13
2.13 (s, 3H, ꢀCH3 of ꢀCOCH3), 2.67 (q, J= 6.6 Hz, 1H, Hꢀ4), 4.94 (d, J= 3.3 Hz, 1H, Hꢀ2). C
NMR (75 MHz, CDCl3): δ 6.50, 14.13, 17.91, 18.28, 18.63, 20.14, 21.12, 28.19, 28.26, 30.04,
30.38, 31.77, 31.89, 32.16, 32.41, 32.90, 34.97, 35.35, 35.58, 36.09, 36.99, 38.41, 39.28, 39.77,
41.14, 42.93, 43.24, 53.10, 53.40, 54.47, 169.69 (ꢀCH3 of ꢀOAc), 207.98 (Cꢀ3). FTIR (nujol, cmꢀ
1): ν 1744, 1720, 1377, 1365, 1257, 1229, 1184, 1164, 1041, 1023, 997, 933, 795, 758, 722.
Analysis calcd: C, 79.29; H, 10.81. Found: C, 77.42; H, 11.03.
4.15.24 Friedelan-3-oximino-2α−ol (25): Yield: 95%, pale yellow plateꢀlike crystals, m.p. 265ꢀ
271 oC (ethanol, lit.26d 266ꢀ272 oC). 1H NMR (300 MHz, DMSOꢀd6): δ 0.71 (s, 3H, Meꢀ24), 0.74

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(s, 3H, Meꢀ25), 0.84 (d, J=2.7 Hz, 3H, Meꢀ23), 0.95 (s, 3H, Meꢀ30), 1.00 (s, 3H, Meꢀ26 and Meꢀ
29), 1.03 (s, 3H, Meꢀ27), 1.18 (s, 3H, Meꢀ28), 1.92ꢀ2.10 (m, 2H, Hꢀ2), 2.50ꢀ2.58 (m, 1H, Hꢀ4),
13
3.62ꢀ 3.80 (m, 1H, Hꢀ2).). C NMR (75 MHz, DMSOꢀd6): δ 8.37, 13.25, 17.69, 17.93, 18.47,
19.86, 27.82 (2ꢀcarbons), 28.55, 28.97, 29.54, 30.08, 31.66, 31.77, 31.86, 32.44, 34.76 (2ꢀ
carbons), 35.56, 36.19, 37.79, 39.46, 39.77, 40.02, 42.35, 44.80, 51.68, 52.60, 57.48, 160.06.
FTIR (nujol, cmꢀ1): ν 3286, 3168, 2724, 1380, 1261, 1147, 1093, 1023, 943, 801, 724.
4.15.25 Friedelane-2α,3β-diacetate (26): Eluent in column chromatography: 1% ethyl acetate
o
o
in petroleum ether. Yield: 97%,white crystalline solid, m.p. 226ꢀ228 C (lit15a 226ꢀ227 C).1H
NMR (300 MHz, CDCl3): δ 0.84 (s, 3H, Meꢀ24), 0.88 (s, 3H, Meꢀ25), 0.91 (s, 3H, Meꢀ23), 0.94
(s, 3H, Meꢀ30), 0.99 (s, 3H, Meꢀ26 and Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.17 (s, 3H, Meꢀ28), 2.06
(s, 3H, ꢀCH3 of ꢀOAc), 2.08 (s, 3H, ꢀCH3 of ꢀOAc), 4.02ꢀ4.4.33 (m, 1H, Hꢀ2), 4.84 (dd, J=21.3
Hz and 2.4 Hz, 1H, Hꢀ3). 13C NMR (75 MHz, CDCl3): δ 10.49, 15.32, 17.67, 18.04, 18.52,
20.06, 21.00, 21.73, 21.29, 28.18, 30.07, 30.41, 31.47, 31.87, 32.14, 32.34, 32.91, 34.97, 35.43,
36.13, 36.50, 37.55, 38.45, 39.29, 39.70, 41.36, 42.93, 43.86, 53.04, 53.17, 70.90, 73.97, 169.63
(ꢀCH3 of C2ꢀOAc), 169.95 (ꢀCH3 of C3ꢀOAc). FTIR (nujol, cmꢀ1): ν 1734, 1717, 1464, 1376,
1243, 1227, 1201, 1032, 965, 891, 719.
4.15.26 3-Chlorofriedel-3-ene (27): Eluent in column chromatography: petroleum ether. Yield:
12%, white cubeꢀlike crystals, m.p. 260ꢀ262 oC.1H NMR (300 MHz, CDCl3): δ 0.77 (s, 3H, Meꢀ
24), 0.87 (m, 3H, Meꢀ25), 0.93 (m, 12H, Meꢀ26, Meꢀ27, Meꢀ29, Meꢀ30), 1.10 (s, 3H, Meꢀ28)
1.63 (d, 3H, J=2.1 Hz, Meꢀ23), 1.80 (dd, 1H, J= 3 Hz, 12 Hz Hꢀ1), 2.23ꢀ2.36 (br m, 2H, Hꢀ2).
13C NMR (75 MHz, CDCl3): δ 13.03 (Cꢀ24), 17.27 (Cꢀ23), 17.27, 17.54 (Cꢀ25), 17.80 (Cꢀ27),
19.04, 19.51(Cꢀ26), 27.18, 29.06, 29.55, 30.82, 31.13, 31.32 (Cꢀ29), 31.88 (Cꢀ28), 33.99, 34.26,
34.38, 34.49 (Cꢀ30), 35.07, 36.02, 37.34, 38.06, 38.27, 38.78, 39.66, 41.94, 51.72, 55.21, 125.83
(Cꢀ3), 138.20 (Cꢀ4). FTIR (neat, cmꢀ1): ν 3409, 2926, 2847, 1444, 1380, 1072, 973.
4.15.27 3-Chlorofriedel-2-ene-2-carbaldehyde (28): Eluent in column chromatography: 5%
o
ethyl acetate in petroleum ether. Yield: 52%, white crystalline solid, m.p. 218 C.1H NMR (300
MHz, CDCl3): δ 0.77 (s, 3H, Meꢀ24), 0.93 (s, 3H, Meꢀ25) 0.94 (s, 3H, Meꢀ30), 0.99 (s, 6H, Meꢀ
26 and Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.14 (s, 3H, Meꢀ28), 1.16 (d, 3H, J=2.4 Hz Meꢀ23), 1.91ꢀ
13
2.05 (m, 2H, Haxꢀ1 and Hꢀ10) 2.39ꢀ2.45 (m, 2H, Heq and Hꢀ4). C NMR (75 MHz, CDCl3): δ
11.77 (Cꢀ23), 14.43 (Cꢀ24), 17.39 (Cꢀ25), 18.31, 18.61 (Cꢀ27), 20.41 (Cꢀ26), 21.53, 28.18,
30.03, 30.27, 31.79 (Cꢀ29), 32.12 (Cꢀ28), 32.43, 32.80, 35.03 (Cꢀ30), 35.17, 35.31, 35.99, 36.79,

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38.17, 38.17, 39.27, 39.66, 41.84, 42.75, 52.88, 53.21, 54.23, 133.08 (Cꢀ2), 155.10 (Cꢀ3), 192.18
(ꢀCHO). FTIR (neat, cmꢀ1): ν 2932, 2855, 1675, 1611, 1394, 1232, 953.
4.15.28 Friedel-2-en-3-ol-2-carbaldehyde (29): Eluent in column chromatography: 7% ethyl
o
acetate in petroleum ether. Yield: 10%, white powdered solid, m.p. 258ꢀ260 C.1H NMR (300
MHz, CDCl3): δ 0.93 (s, 3H, Meꢀ24), 0.94 (s, 3H, Meꢀ25), 0.986 (s, 3H, Meꢀ26), 0.994 (s, 3H,
Meꢀ29), 1.01 (s, 3H, Meꢀ30), 1.14 (s, 3H, Meꢀ27), 1.18 (s, 3H, Meꢀ28), 1.79ꢀ1.85 (m, 1H, Haxꢀ
1), 1.99ꢀ 2.07 (m, 3H, Meꢀ23), 2.37ꢀ 2.52 (m, 1H, Heq1), 2.64 (dd, 1H, J= 3 Hz and 18 Hz, Hꢀ4),
9.97 (d, 1H, J= 4.8 Hz, ꢀCHO). 13C NMR (75 MHz, CDCl3): δ 16.52 (CH3ꢀ23), 17.63 (CH3ꢀ24),
18.10 (CH3ꢀ25), 18.51, 18.78 (CH3ꢀ27), 20.10 (CH3ꢀ26), 28.14, 28.14, 30.01, 30.20, 31.79 (CH3ꢀ
29), 32.11, 32.16, 32.74 (CH3ꢀ28), 34.60, 34.64, 34.99 (CH3ꢀ30), 35.31, 35.88, 36.85, 38.23,
38.42, 39.21, 39.70, 42.76, 42.76, 52.44, 54.59, 129.02 (Cꢀ2), 166.02 (Cꢀ3), 192.02 (ꢀCHO).
FTIR (KBr, cmꢀ1): ν 3443, 2933, 2863, 1687, 1587, 1462, 1383, 1282, 1177, 972, 675, 628, 573.
Analysis calcd: C, 81.88; H, 11.08. Found: C, 81.40, H, 11.05.
4.15.29 3-Chlorofriedel-2-en-4α-ol-2-carbaldehyde (30): Eluent in column chromatography:
10% ethyl acetate in petroleum ether. Yield: 7ꢀ65%, white powdered solid, m.p. 195 oC.1H NMR
(300 MHz, CDCl3): δ 0.90 (s, 3H, Meꢀ25), 0.94 (s, 3H, Meꢀ30), 0.97 (s, 3H, Meꢀ24), 1.00 (s, 6H,
Meꢀ26 and Meꢀ29), 1.01 (s, 3H, Meꢀ27), 1.18 (s, 3H, Meꢀ28), 1.40 (s, 3H, Meꢀ23), 1.94ꢀ 2.14
(m, 3H, Hꢀ6 and Hꢀ10), 2.41 (dd, J= 4.2 Hz & 18.3 Hz, 2H, Hꢀ1), 10.24 (s, 1H, ꢀCHO). 13C
NMR (75 MHz, CDCl3): δ 17.42 (CH3ꢀ24), 17.89 (CH3ꢀ25), 17.98 (CH3ꢀ23), 18.70 (CH3ꢀ27),
20.43 (CH3ꢀ26), 20.66, 22.03, 28.16, 30.02, 30.26, 31.74 (CH3ꢀ29), 32.09 (CH3ꢀ28), 32.39,
32.76, 33.59, 35.03 (CH3ꢀ30), 35.32, 35.40, 35.96, 36.61, 38.13, 39.26, 39.66, 42.60, 42.71,
46.43, 52.04, 78.4 (Cꢀ4), 133.7 (Cꢀ2), 153.2 (Cꢀ3) 192.8 (ꢀCHO). FTIR (neat, cmꢀ1): ν 3480,
2926, 2855, 1675, 1373, 1113, 945.
4.15.30 Friedel-3-en-23-al (31): Eluent in column chromatography: petroleum ether. Yield:
o
56%, white smallꢀneedleꢀshaped crystals, m.p. 232 C. (petroleum etherꢀethyl acetate). 1H NMR
(300 MHz, CDCl3): δ 0.88 (s, 3H, Meꢀ25), 0.95 (s, 3H, Meꢀ30), 1.00 (s, 6H, Meꢀ26 and Meꢀ29),
1.01 (s, 3H, Meꢀ27), 1.15 (s, 3H, Meꢀ24), 1.18 (s, 3H, Meꢀ28), 2.26ꢀ 2.52 (m, 3H, Hꢀ1 and Hꢀ
10), 2.72 (td, J= 3Hz and 15 Hz, 1H, Heqꢀ2), 6.55 (d, J=2.7 Hz, 1H, Hꢀ3), 9.30 (s, 1H, ꢀCHO).
13C NMR (75 MHz, CDCl3): δ 16.73 (Cꢀ24), 17.96 (Cꢀ25), 18.33 (Cꢀ27), 18.62, 20.05 (Cꢀ26),
21.12, 28.19, 28.87, 30.07, 30.57, 31.83 (Cꢀ29), 32.14 (Cꢀ28), 32.27, 32.86, 35.03 (Cꢀ30), 35.39,
35.51, 36.07, 37.28, 37.54, 37.93, 38.37, 39.29, 39.77, 42.93, 53.09, 56.95, 151.84 (Cꢀ3), 151.98

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(Cꢀ4), 194.23 (ꢀCHO). FTIR (KBr, cmꢀ1): ν 3449, 2929, 2862, 2713, 1680, 1628, 1455, 1384,
1170, 1042, 991, 825, 690. LRESIMS m/z (%): 447.3 (87) [M+ Na]+, 413.2 (64), 301.1 (100).
Analysis calcd: C, 84.84; H, 11.39. Found: C, 84.38, H, 11.17.
4.15.31 Friedelan-3α,4α-epoxide(32): Eluent in column chromatography: petroleum ether.
Yield: 56%, white powdered solid, m.p. 276 oC.1H NMR (300 MHz, CDCl3): δ 0.82 (s, 3H, CH3ꢀ
25), 0.934 (s, 3H, CH3ꢀ24), 0.944 (s, 3H, CH3ꢀ30), 0.99 (d, J= 1.8 Hz, 3H, CH3ꢀ26), 1.00 (s, 3H,
CH3ꢀ29), 1.02 (s, 3H, CH3ꢀ27), 1.17 (s, 3H, CH3ꢀ28), 1.26 (s, 3H, CH3ꢀ23), 2.19 (q, J= 6.6 Hz,
1H, Haxꢀ2), 2.89 (br s, 1H, Heqꢀ2), 4.221 (t, J= 3 Hz, 1H, Hꢀ3).13C NMR (75 MHz, CDCl3):
δ 9.52 (CH3ꢀ23), 15.23 (CH3ꢀ24), 17.68 (CH3ꢀ25), 18.20 (CH3ꢀ7), 18.64 (CH3ꢀ27), 20.00 (CH3ꢀ
26), 23.81 (Cꢀ1), 28.16 (Cꢀ20), 30.01 (Cꢀ17), 30.51 (Cꢀ12), 31.79 (CH3ꢀ29), 32.13 CH3ꢀ28),
32.29 (Cꢀ21), 32.83 (Cꢀ15), 34.99 (CH3ꢀ30), 35.24 (Cꢀ19), 35.31 (Cꢀ11), 36.03 (Cꢀ16), 36.41 (Cꢀ
9), 38.36 (Cꢀ14), 39.25 (Cꢀ22), 39.72 (Cꢀ13), 40.73 (Cꢀ6), 41.78 (Cꢀ2), 42.87 (Cꢀ18), 50.42 (Cꢀ
5), 52.83 (Cꢀ10), 53.36 (Cꢀ8), 76.88 (Cꢀ3), 102.35 (Cꢀ4). FTIR (KBr, cmꢀ1): ν 2919, 2850, 1466,
1376, 1309, 723, 655. Analysis calcd: C, 84.44; H, 11.81. Found: C, 84.66, H, 11.95.
4.15.32 24-Norfriedel-1, 3, 5 (10), 6-tetraene (33): Eluent in column chromatography:
petroleum ether. Yield: 42%, colourless sticky gum.1H NMR (300 MHz, CDCl3): δ 0.97 (s, 3H,
CH3ꢀ30), 1.02 (s, 6H, Meꢀ26 and CH3ꢀ29), 1.03 (s, 3H, CH3ꢀ27), 1.21 (d, J= 2.4 Hz, CH3ꢀ28),
1.25 (d, J= 4.2 Hz, CH3ꢀ25), 2.25 (d, J= 3Hz, CH3ꢀ23), 6.06 (dd, 1H, J= 2.7Hz and 9.9 Hz, Hꢀ7),
13
6.83 (dd, 1H, J= 3.0 Hz and 9.9 Hz, Hꢀ6), 6.92ꢀ7.17 (m, 3H, Hꢀ1, Hꢀ2 and Hꢀ3). C NMR (75
MHz, CDCl3): δ 15.01 (Cꢀ25), 18.81 (Cꢀ27), 20.45 (Cꢀ26), 21.80, 21.85, 21.22 (Cꢀ23), 30.29,
30.96, 31.49, 31.61 (Cꢀ29), 32.09 (Cꢀ28), 32.22, 33.02, 34.77, 35.37 (Cꢀ30), 35.73, 37.69, 38.00,
38.94, 39.36, 42.83, 47.93, 119.14, 124.95, 128.98, 130.95, 131.13, 131.84, 133.87, 147.12.
LRESIMS m/z (%): 413.4 (95) [M+ Na]+. Analysis calcd: C, 89.16; H, 10.84. Found: C, 88.97;
H, 11.01.
4.15.33 3-Chlorofriedel-2-ene-2-carboxaldoxime (34): Yield: 96%, offꢀwhite needleꢀshaped
o
1
crystals, m.p. 164 C (chloroformꢀmethanol). H NMR (300 MHz, CDCl3): δ 0.78 (s, 3H, Meꢀ
24), 0.93 (s, 3H, Meꢀ25), 0.94 (s, 3H, Meꢀ30), 0.99 (s, 6H, Meꢀ26 and Meꢀ29), 1.01 (s, 3H, Meꢀ
27), 1.09 (d, J= 7.2 Hz, 3H, Meꢀ23), 1.17 (s, 3H, Meꢀ28), 1.92 (d, J= 13.2 Hz, 1H, Hꢀ1), 2.13 (dt,
J= 3.3 Hz & 12.9 Hz, 1H, Hꢀ4), 2.31ꢀ2.45 (m, 2H, Hꢀ10), 8.40 (s, 1H, ꢀCH=NOH). 13C NMR (75
MHz, CDCl3): δ 12.47 (CH3ꢀ23), 14.28 (CH3ꢀ24), 17.39 (CH3ꢀ25), 18.33, 18.63 (CH3ꢀ27), 20.43
(CH3ꢀ26), 23.09, 28.17, 30.02, 30.35, 31.77 (CH3ꢀ29), 32.10, 32.41, 32.77 (CH3ꢀ28), 35.06

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(CH3ꢀ30), 35.15, 35.35, 35.97, 36.73, 38.04, 38.18, 39.26, 39.65, 41.81, 42.74, 52.32, 52.87,
54.32, 126.29 (Cꢀ2), 141.69 (Cꢀ3), 150.28 (ꢀC=NOH). FTIR (KBr, cmꢀ1): ν 3353, 2931, 2862,
1623, 1458, 1386, 1294, 1182, 1135, 985, 958, 749, 549. LRESIMS m/z (%): 488.5 (68) [M+
H]+, 474.5 (100). Analysis calcd: C, 76.27; H, 10.32; N, 2.87. Found: C, 76.47; H, 10.41; N,
2.77.
4.15.34 3-Chlorofriedel-2-ene-2-methanol (35): Eluent in column chromatography: 15% ethyl
o
acetate in petroleum ether. Yield 92%, white crystalline solid, m.p. 244ꢀ246 C (chloroformꢀ
methanol). 1H NMR (300 MHz, CDCl3): δ 0.77 (s, 3H, Meꢀ24), 0.79 (s, 3H, Meꢀ25), 0.93 (s, 3H,
Meꢀ23), 0.94 (s, 3H, Meꢀ30), 0.99 (s, 3H, Meꢀ27), 1.01 (d, J=2.1 Hz, 6H, Meꢀ26 and 29), 1.17
(d, J= 3 Hz, 3H, Meꢀ28), 1.90 (dd, J= 3 Hz and 10.5 Hz, 1H, Hꢀ1), 2.07ꢀ2.27 (m, 3H, Hꢀ1, Hꢀ4
and Hꢀ10), 4.25 (dd, J= 12 Hz and 26.7 Hz, 2H, ꢀCH2OH). 13C NMR (75 MHz, CDCl3): δ 12.43
(CH3ꢀ23), 14.09 (CH3ꢀ24), 17.49 (CH3ꢀ25), 18.37, 18.64 (CH3ꢀ27), 20.39 (CH3ꢀ26), 26.05,
28.19, 30.04, 30.35, 31.80 (CH3ꢀ29), 32.12 (CH3ꢀ28), 32.42, 32.82, 35.04 (CH3ꢀ30), 35.33,
36.01, 36.69, 37.97, 38.20, 39.28, 39.68, 41.87, 42.77, 51.31, 52.87, 54.96, 64.07 (ꢀCH2OH),
132.14 (Cꢀ2), 133.10 (Cꢀ3). FTIR (KBr, cmꢀ1): ν 3384, 2938, 2864, 1662, 1461, 1385, 1183,
1133, 1045, 1007, 948, 755, 696. LRESIMS m/z (%): 499.5 (40) [M + Na + 2H]+, 497.5 (100)
[M + Na]+, 413.4 (44), 301.2 (75). Analysis calcd: C, 78.35; H, 10.82. Found: C, 78.47, H,
10.91.
4.15.35 3-Chlorofriedel-2-ene-2-methanol acetate (36): Eluent in column chromatography: 2%
o
ethyl acetate in petroleum ether. Yield 98%, white crystalline solid, m.p. 180ꢀ182 C (pet. etherꢀ
ethyl acetate). 1H NMR (300 MHz, CDCl3): δ 0.77 (s, 3H, Meꢀ24), 0.92 (s, 3H, Meꢀ25), 0.94 (s,
3H, Meꢀ23), 1.00 (s, 3H, Meꢀ30), 1.01 (s, 6H, Meꢀ26 and Meꢀ29), 1.06 (s, 3H, Meꢀ27), 1.17 (s,
3H, Meꢀ28), 1.90 (d, J= 13.2 Hz, 1H, Hꢀ1), 2.09 (s, 3H, ꢀCH3 of ꢀOAc), 4.75 (s, 2H, ꢀCH2OH).
13C NMR (75 MHz, CDCl3): δ 12.38 (CH3ꢀ23), 14.09 (CH3ꢀ24), 17.45 (CH3ꢀ25), 18.33, 18.58
(CH3ꢀ27), 20.33 (CH3ꢀ26), 20.87, 25.67, 28.15, 30.03, 30.26, 31.82 (CH3ꢀ29), 32.10 (CH3ꢀ28),
32.38, 32.83, 34.96 (CH3ꢀ30), 35.20, 35.32, 35.99, 36.66, 37.89, 38.20, 39.23, 39.67, 41.83,
42.82, 51.39, 52.83, 54.75, 65.30 (ꢀCH2OAc), 127.69 (Cꢀ2), 134.98 (Cꢀ3), 171.02 (ꢀOCOCH3).
FTIR (KBr, cmꢀ1): ν 3444, 2933, 2866, 1745, 1459, 1383, 1225, 1026, 954, 910, 759. LRESIMS
m/z (%): 541.5 (40) [M + Na + 2H]+, 539.5 (100) [M + Na]+, 301.3 (38).Analysis calcd: C,
76.63; H, 10.33; O, 6.19. Found: C, 76.67; H, 10.25; O, 6.05.

Page 29 of 37
New Journal of Chemistry
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DOI: 10.1039/C8NJ00009C
4.15.36 3-Chlorofriedel-2-ene-2-carboxamide (37): Eluent in column chromatography: 10%
o
ethyl acetate in petroleum ether. Yield: 58%, pale yellow crystals, m.p. 233ꢀ236 C (pet. etherꢀ
ethyl acetate). 1H NMR (300 MHz, CDCl3): δ 0.94 (s, 3H, Meꢀ24), 0.96 (s, 3H, Meꢀ25), 0.97 (s,
3H, Meꢀ23), 0.99 (s, 3H, Meꢀ30), 1.005 (s, 3H, Meꢀ27), 1.014 (s, 6H, Meꢀ26 and Meꢀ29), 1.17
(s, 3H, Meꢀ28), 1.99 (d, J= 12.3 Hz, 1H, Hꢀ1), 5.08 (s, 1H, ꢀCONH2), 5.48 (s, 1H, ꢀCONH2). 13C
NMR (75 MHz, CDCl3): δ 16.7 (CH3ꢀ24), 17.49 (CH3ꢀ25), 17.53 (CH3ꢀ23), 19.35 (CH3ꢀ27),
21.57 (CH3ꢀ26), 26.58, 27.16, 28.69, 29.03, 29.25, 30.84, 31.12, 31.37, 31.87 (CH3ꢀ29), 33.95
(CH3ꢀ28), 34.04, 34.29, 35.02 (CH3ꢀ30), 36.16, 37.24, 38.24, 38.65, 38.65, 39.38, 41.83, 44.05,
51.82, 52.20, 132.02 (Cꢀ2), 153.58 (Cꢀ3), 161.70 (ꢀCONH2). Analysis calcd: C, 76.27; H, 10.32;
N, 2.87; O, 3.28. Found: C, 75.57; H, 10.66; N, 2.90; O, 3.35.
4.15.37 3-Chlorofriedel2-en-4α-ol-2-carboxaldoxime (38): Yield 97%, pale yellow crystals,
m.p. 240 oC (chloroformꢀmethanol). 1H NMR (300 MHz, CDCl3): δ 0.92 (s, 3H, Meꢀ25), 0.94 (s,
3H, Meꢀ30), 0.98 (s, 3H, Meꢀ24), 1.00 (s, 3H, Meꢀ27), 1.01 (s, 6H, Meꢀ26 and Meꢀ29), 1.18 (s,
3H, Meꢀ28), 1.35 (s, 3H, Meꢀ23), 1.95ꢀ 2.19 (m, 4H, Hꢀ6 and Hꢀ10), 2.46 (dd, J= 4.5 Hz and
17.7 Hz, 2H, Hꢀ1), 8.37 (s, 1H, ꢀCH=NOH). 13C NMR (75 MHz, CDCl3): δ 17.43 (CH3ꢀ24),
17.89 (CH3ꢀ25), 18.04 (CH3ꢀ23), 18.72 (CH3ꢀ27), 20.43 (CH3ꢀ26), 21.30, 23.50, 28.17, 30.03,
30.30, 31.75 (CH3ꢀ29), 32.09 (CH3ꢀ28), 32.37, 32.75, 33.59, 35.03 (CH3ꢀ30), 35.32, 35.47,
35.96, 36.59, 38.15, 39.25, 39.67, 42.56, 42.72, 46.56, 52.05, 77.97 (Cꢀ4), 128.70 (Cꢀ2), 141.20
(Cꢀ3), 150.15 (C=NOH). FTIR (KBr, cmꢀ1): ν 3422, 2939, 2868, 1627, 1459, 1385, 1295, 1181,
1073, 992, 972, 751, 696. LRESIMS m/z (%): 526.5 (100) [M + Na]+, 413.5 (48).Analysis calcd:
C, 73.85; H, 10.00; N, 2.78; O, 6.35. Found: C, 73.87; H, 10.16; N, 2.90, O, 6.01.
4.15.38 3-Chlorofriedel-2-en-4α-ol-2-methanol (39): Eluent in column chromatography: 25%
o
ethyl acetate in petroleum ether. Yield 78%, pale yellow crystals, m.p. 160 C.1H NMR (300
MHz, CDCl3): δ 0.87 (s, 3H, Meꢀ25), 0.91 (s, 3H, Meꢀ24), 0.95 (s, 3H, Meꢀ30), 1.00 (s, 9H, Meꢀ
26, Meꢀ27 and Meꢀ29), 1.15 (s, 3H, Meꢀ28), 1.26 (s, 3H, Meꢀ23), 1.75 (s, 3H, Meꢀ23), 1.87ꢀ
1.91 (m, 3H, Hꢀ1 and Hꢀ10), 4.19 (s, 2H, ꢀCH2OH). 13C NMR (75 MHz, CDCl3): δ 14.15 (CH3ꢀ
24), 18.14 (CH3ꢀ25), 18.62 (CH3ꢀ27), 19.04 (Cꢀ23), 20.05 (CH3ꢀ26), 27.13, 28.16, 29.71, 30.02,
30.45, 31.81 (CH3ꢀ29), 32.13 (CH3ꢀ28), 32.26, 32.78, 35.01 (CH3ꢀ30), 35.16, 35.30, 35.98,
36.48, 38.30, 38.47, 39.24, 39.77, 41.55, 42.83, 50.43, 52.59, 70.27 (ꢀCH2OH), 77.21 (Cꢀ4),
128.95 (Cꢀ2), 144.11 (Cꢀ3).