Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

Article abstract of DOI:10.1002/anie.201916613

Presented here is a concise synthesis of secu′amamine A, and fluvirosaones A and B from readily available allosecurinine and viroallosecurinine. The key C2-enamine derivative of (viro)allosecurinine, the presumed biosynthetic precursors of these natural products, was accessed, for the first time, by a VO(acac)₂-mediated regioselective Polonovski reaction. Formal hydration and 1,2-amine shift of this pluripotent enamine compound afforded secu′amamine A. Formal oxidative [3+2] cycloaddition reaction between this enamine and TMS-substituted methallyl iodide reagent paved the way to the precursors of fluvirosaones A and B. The relative stereochemistry at the C2 position of these advanced intermediates governs the fate of 1,2-amine shift leading to fluvirosaones A and B. The syntheses of potential biosynthetic precursors and investigations of their chemical reactivities have provided insights regarding the biogenesis of these natural products.

Full text of DOI:10.1002/anie.201916613

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Accepted Article
Title: Biosynthetically Inspiring Synthesis of Secu’amamine A,
Fluvirosaones A and B
Authors: Sanghyeon Lee, Gyumin Kang, Garam Chung, Dongwook
Kim, Hee-Yoon Lee, and Sunkyu Han
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Angewandte Chemie International Edition
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RESEARCH ARTICLE
Biosynthetically Inspiring Synthesis of Secu’amamine A,
Fluvirosaones A and B
Sanghyeon Lee,[a]# Gyumin Kang,[a][b]# Garam Chung, Dongwook Kim, Hee-Yoon Lee,* and
[a]
[b]
[a]
Sunkyu Han*[a][b]
#
These authors contributed equally.
[
[
a]
b]
S. Lee, G. Kang, G. Chung, Dr. H.-Y. Lee, Dr. S. Han
Department of Chemistry
Korea Advanced Institute of Science and Technology (KAIST)
291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
E-mail: sunkyu.han@kaist.ac.kr, leehy@kaist.ac.kr
G. Kang, Dr. D. Kim, Dr. S. Han
Center for Catalytic Hydrocarbon Functionalizations
Institute for Basic Science (IBS)
291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
Supporting information for this article is given via a link at the end of the document.
Abstract: We present a concise synthesis of secu’amamine A,
As a means to maximize selective advantages, organisms
often diversify the structure of certain secondary metabolites to
structurally more complex molecules by the action of various
enzymes and inherent chemical reactivity of biosynthetic
intermediates. Securinega alkaloids are one of many families of
natural products that display an array of structural diversity.
Specifically, the molecular evolution of monomeric tetracyclic
congeners such as norsecurinine (1, Scheme 1), virosecurinine
(2), allosecurinine (3), or viroallosecurinine (4) provides the
platform for such diverse complex molecules. One
representative mode of diversification of securinega precursors
fluvirosaones A and B from readily available allosecurinine and
viroallosecurinine.
viro)allosecurinine, the presumed biosynthetic precursors of these
natural products, was accessed, for the first time, by a VO(acac)
mediated regioselective Polonovski reaction. Formal hydration and
,2-amine shift of this pluripotent enamine compound afforded
The
key
C2-enamine
derivative
of
(
2
-
1
secu’amamine A. On the other hand, formal oxidative [3+2]
cycloaddition reaction between this enamine and TMS-substituted
methallyl iodide reagent paved the way to the assumed biosynthetic
precursors of fluvirosaones A and B. We demonstrated that the
relative stereochemistry at the C2 position of these advanced
intermediates governs the fate of 1,2-amine shift leading to
fluvirosaones A and B, respectively. While our synthetic design was
inspired by the biosynthetic hypothesis of these natural products,
syntheses of potential biosynthetic precursors and investigations of
their chemical reactivity inversely have provided insights regarding
the biogenesis of these natural products.
is
a
Rauhut–Currier reaction-based carbon–carbon bond
3
formation exemplified by our recent total synthesis of
flueggenine C (5).4 The other notable mode of derivatization
involves oxidation(s). An oxidation of the tertiary amine moiety of
the securinega precursors would yield the N-oxide derivative (I)
that serves as a branching point to various high-oxidation state
securinega alkaloids. For example,
a
Meisenheimer
5
rearrangement of I yields phyllantidine (7). Further oxidation of
N-oxide I to nitrone II and subsequent [1,3]-dipolar cycloaddition
reactions yield flueggine A (8),6,7 virosaines A (9),8,9 and B (10).6
Other important yet unexplored modes of diversification stem
from enamine III. Natural products such as securigine D (11),
Introduction
Synthetic chemists have been inspired by the biosynthesis
of natural products. Thorough studies on the biosynthetic
pathways or intuitively proposed biogenetic hypotheses of
natural products have guided synthetic chemists to devise
efficient biomimetic approaches toward the target molecules.1
However, elucidation of the exact biosynthetic pathway can be
cumbersome due to challenges associated with the expression
and purification of key enzymes as well as difficulties in the
isolation of practically useful amount of biosynthetic
intermediates. On the other hand, synthetic chemists can utilize
the whole periodic table to efficiently access proposed key
biosynthetic intermediates, study their reactivity, and thus
provide the biosynthetic community with invaluable information.2
secu’amamine
A
(12), fluvirosaones
A
(13),
B
(14),
flueggeacosine A (15), and suffruticosine (16) are presumed to
be derived from enamine III. Despite its potential synthetic utility
and biosynthetic significance, selective access to III has been
hampered by preferential C6-iminium formation from either
securinega precursors10 or N-oxide I (vide infra).11 In this report,
we describe the development of C2-selective Polonovski
reaction of N-oxide I to enamine III, and its transformation to
secu’amamine A (12), fluvirosaones A (13), and B (14).
Secu’amamine A (12) consists of an atypical aza-bicyclo-
3,3,1]-nonane core structure.12 This unique 1,2-amine shift-
based framework presents interesting (bio)synthetic questions.
[
1
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RESEARCH ARTICLE
Scheme 1. Biosynthetically relevant derivatizations of securinega alkaloids.
Even though there have been model studies hinting at a potential
1
Results and Discussion
,2-amine shift during the biosynthesis of this natural product,13
its execution in a real system has been elusive due to the
difficulty in accessing the C3-oxidized securinega derivative.
Hence, despite two previous elegant total syntheses of this
natural product,14,15 key questions regarding the biosynthetically
relevant 1,2-amine shift have remained unanswered.
Fluvirosaones A (13) and B (14), pentacyclic securinega
alkaloids recently isolated from Flueggea virosa, consist of a
cyclopentenone E-ring that is constructed by two carbon–carbon
bonds formation between the external three carbon unit and the
base securinega structure. The α-tertiary amine moiety in the
E-ring poses added synthetic challenge. It is important to note
that unlike the aforementioned high-order and high-oxidation
state securinega alkaloids, the biosynthetic mode of assembly of
the E- ring in fluvirosaones A (13) and B (14) is not obvious.
Design of the Synthesis
Our synthetic design of fluvirosaones A (13) and B (14) laid
its foundation on the configurational analysis at C2 of
fluvirosaone A (13) and C3 of fluvirosaone B (14, Scheme 2).
Stereoelectronic analysis of these two natural products revealed
that 1,2-amine shift of fluvirosaone A (13) would provide 3-epi-
fluvirosaone B (17) and not fluvirosaone B (14). By the same
token, fluvirosaone B (14) can only be accessed from 2-epi-
fluvirosaone A (18). Gu and coworkers rationalized different
atom connectivity and mismatching stereochemical relationship
between fluvirosaones A (13) and B (14) by two parallel
biogenetic pathways that diverge in the early stage from
virosecurinine and involve analogous enzymatic reactions
(Scheme S1).16 As an alternative biosynthetic scenario, absence
of 2-epi-fluvirosaone A (18) and 3-epi-fluvirosaone B (17) in
nature led us to conjecture that fluvirosaone A (13) and 2-epi-
fluvirosaone A (18) are simultaneously generated from a
1
6
Furthermore, fluvirosaones
B
(14) also possesses the
rearranged aza-bicyclo-[3,3,1]-nonane core structure. These
structural aspects raise interesting questions regarding the
biogenetic origins of two closely related natural products. These
structural and biosynthetic features of secu’amamine A (12),
fluvirosaones A (13) and B (14) as well as our interest in
biosynthetically inspired synthesis of natural products17–20 led us
to initiate a synthetic program aiming for these natural products
from readily available securinega precursors.
common
biosynthetic
intermediate
by
a
late-stage
stereodivergent cyclization, and only 2-epi-fluvirosaone A (18)
would be spontaneously transformed to fluvirosaone B (14).
Based on this assumption, we planned to access both
fluvirosaone A (13) and 2-epi-fluvirosaone A (18) by developing
2
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RESEARCH ARTICLE
Scheme 2. Retrosynthetic analysis of secu’amamine A, fluvirosaones A and B.
a stereodivergent [3+2]-cycloaddition between enamine 20 and
Our initial grand challenge was the regioselective oxidation
of allosecurinine (3) to enamine 20 (Scheme 3). Chen’s oxidation
studies of securinine indicated that C6-oxidation of
allosecurinine (3) would be favorable over C2-oxidation under
brominative oxidation conditions.10 To overturn this inherent
selectivity, we explored a Polonovski reaction that has been
widely utilized for the alpha oxidation of amine to generate
iminium ions and has enabled further transformations in alkaloid
syntheses.23,24 Structural analysis of allosecurinine (3) enabled
us to identify that C2 methine proton of allosecurinine N-oxide
(22) is syn-periplanar to its N-oxide oxygen. Inspired by
Andrade’s studies that discussed the competition between
intramolecular syn- and intermolecular anti-elimination for the
Polonovski reaction of Strychnos alkaloids,25 we initially
conducted Polonovski reaction using TFAA as an activating
agent. When N-oxide derivative 22, obtained by m-CPBA-
mediated oxidation of allosecurinine (3), was treated with TFAA
and subsequently with potassium cyanide, C6-cyanoamine 25
1,3-dipole 19, an underexplored combination of partners for the
construction of five-membered carbocycles. We envisioned that
secu’amamine A (12) can also be accessed from enamine 20.
We planned to synthesize secu’amamine
stereospecific 1,2-amine shift of (3S)-3-hydroxyallosecurinine
21). Alcohol 21 would be derived from the pluripotent enamine
0. We envisioned accessing enamine 20 by establishing a
A (12) via a
(
2
method for the C2-selective Polonovski reaction over the
inherently favored C6-iminium formation from the N-oxide
derivative of allosecurinine (I, Scheme 1). Commercially
available allosecurinine (3) would be a precursor to natural
secu’amamine A (12) and enantiomers of fluvirosaones A (13)
and
B (14). For the synthesis of natural antipodes of
fluvirosaones A (13) and B (14), we planned to access
viroallosecurinine (4) via total synthesis.21,22
Regioselective Oxidation of Allosecurinine
Scheme 3. Regioselective oxidations of allosecurinine.
3
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RESEARCH ARTICLE
was obtained as the sole product in 48% yield. This observation
implied that trifluoroacetylated N-oxide 23 underwent an E2
Access to enamine 20 put us in a prime position to explore the
biomimetic synthesis of secu’amamine A (12). In an endeavor to
introduce an oxygen atom at the C3 position, we allowed
enamine 20 to react with dimethyldioxirane (DMDO) to obtain
epoxide intermediate 31 and subsequently treated the reaction
mixture with silica gel to produce ketone 32 as a single
diastereomer. Interestingly, exposure of ketone 32 to air resulted
in rapid formation of oxidative fragmentation product 34 in 24%
yield from enamine 20 (Scheme 4). Formation of lactam 34 from
ketone 32 can be rationalized by initial air oxidation at C2
(
anti) elimination by the external base to yield C6 iminium ion 24.
Simple heating of N-oxide derivative 23 produced
trifluoroacetylated enamine 27 in 69% yield via the same iminium
ion intermediate 24 and tautomeric enamine intermediate 26.
To remedy this regioselectivity issue, we envisioned an
activating agent for Polonovski reaction that can also act as an
internal base for the desired syn-selective elimination. To our
delight, treating the N-oxide derivative of allosecurinine 22 with
stoichiometric amount of vanadyl acetylacetonate26 furnished
the long-sought C2-oxidized enamine 20 in 61% yield as a major
product. The formation of enamine 20 connoted access to C2-
iminium ion intermediate 29 via the vanadium-mediated
intramolecular syn elimination by a deprotonation at C2 of
intermediate 28. The rest of the mass balance of this 2-step
transformation consisted of unreacted allosecurinine (3, 13%)
and dimeric enamine 30 (25%). The formation of dimeric
enamine 26 indicates that intermediate 28 undergoes not only
syn elimination but also partial anti elimination to yield C5,C6-
unsaturated enamine intermediate 26. Enamine 26 exhibits
higher nucleophilicity than enamine 20 presumably due to less
steric hindrance and hence undergoes addition to iminium ion 24
present in the reaction mixture. Notably, the formation of
trifluoroacetylated adduct 27 from N-oxide 22 under standard
Polonovski–Potier reaction conditions is consistent with the high
reactivity of enamine intermediate 26. In any case, to the best of
our knowledge, this is the first example of C2-selective oxidation
of the securinega framework. This discovery not only set the
stage for the synthesis of secu’amamine A (12), fluvirosaones A
followed by intramolecular cyclization of the resulting
hydroperoxide intermediate to produce dioxetane 33.2
7,28
The
dioxetane moiety in 33 can then undergo a ring opening and be
transformed to the lactam and carboxylic acid moiety present in
2
9
34. Notably, recently isolated natural product flueggeacosine B
(35)30 consists of the molecular framework of 34 and hints at the
plausibility of similar oxidative ring cleavage event during its
biosynthesis. Furthermore, experimentally discovered inherent
chemical propensity of ketone 32 to undergo facile air oxidation
and subsequent bond scission undermined the originally
proposed biosynthetic pathway of fluvirosaone A (13) that goes
through the C2-epimer of ketone 32 (Scheme S1).16
After noticing the air-sensitivity of ketone 32, we planned
to intercept epoxide intermediate 31 by an in-situ reduction. After
the addition of DMDO to enamine 20, the resulting reaction
3 2
mixture was treated with BF ·OEt to ensure the epoxide
opening and iminium ion formation. Subsequent addition of
sodium cyanoborohydride to the reaction mixture resulted in
(3S)-3-hydroxyallosecurinine (21) in 69% yield. The hydroxyl
group in 21 was consecutively trifluoroacetylated to set the stage
for the 1,2-amine shift. To our pleasure, heating the acetonitrile
solution of trifluoroacetate derivative 36 afforded rearranged
product 38. We propose aziridinium ion 37 as the intermediate
to 38 during this biosynthetically relevant transformation.13
Finally, methanolysis of the trifluoroacetyl moiety in 38 produced
(
13) and B (14) but has also provided the synthetic foundation
for other high-order securinega alkaloids such as securigine D
11), flueggeacosine A (15), and suffruticosine (16).
(
Synthesis of ()-Secu’amamine A
(
–)-secu’amamine A (12) in 53% yield over three steps. Our
Scheme 4. Synthesis of (–)-secu'amamine A.
4
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RESEARCH ARTICLE
spectroscopic data of synthetic (–)-12 matched those of natural
observed products arising from undesired intramolecular
Michael addition reaction. For example, treatment of ketone 46
with potassium carbonate in ethanol solution afforded
1
2
12.
Our
successful
transformation
of
(3S)-3-
hydroxyallosecurinine (21) to (–)-secu’amamine A (12) provides
experimental credence to Magnus’ biosynthetic proposal of this
natural product.13 While our synthetic access to (3S)-3-
hydroxyallosecurinine (21, a potential natural product yet to be
discovered) from enamine 20 suggests the intermediacy of this
enamine intermediate during the biosynthesis of secu’amamine
A (12), we cannot rule out an enzyme mediated direct C3
oxidation of allosecurinine (3).
consecutive acetal formations terminated by
a conjugate
addition at C13 to yield ethanol adduct 47 as the only isolable
product in 69% yield.
As an alternative approach to assemble the five-membered
E-ring, we envisioned a [3+2] cycloaddition between the
enamine moiety of 20 and a carbon-based 1,3-dipole. Although
various synthetic routes toward substituted five-membered
carbocyclic system are reported due to its synthetic utility, there
are only a few reports that utilize enamine and three-carbon
based 1,3-dipole as building blocks to access nitrogen
substituted cyclopentanes.31–33 After extensive experimentation,
we discovered that TMS-functionalized methallyl iodide 48 was
the optimal 1,3-dipole that can be paired with enamine 20 for a
one- or two-step cycloadditive transformation (Scheme 6). When
we treated enamine 20 with TMS-functionalized methallyl iodide
derivative 48 in the presence of silver carbonate, mono-
methallylated enamine 50 (66%) was isolated along with bis-
methallylated pentacycle 49 (8%). The formation of pentacycle
49 was notable because it demonstrated the plausibility of the
formation of fluvirosaone A skeleton by an intramolecular
nucleophilic trapping of the C2 iminium ion by the TMS-allyl
moiety. In fact, treatment of TMS allyl derivative 50 with TFA
provided pentacyclic product 52 in 78% yield. The structure of 52
was corroborated by a single crystal X-ray analysis. Although
both iminium ion 51 and its C3-epimer can be generated by a
fast and reversible protonation, irreversible cyclization of
intermediate 51 from the convex face was preferred.
Construction of the E-ring of Fluvirosaones A and B
We next set out to synthesize fluvirosaones A (13) and B
(
14). The remaining synthetic challenge associated with these
two natural products was the assembly of the five-membered
carbocycle. We initially pursued this objective from ketone 32.
Exposure of ketone 32 to ketophosphonate 39 in the presence
of sodium hydride under strictly anaerobic conditions yielded
another ring-opened tricyclic lactam 42 in 20% yield over two
steps as the sole isolable product (Scheme 5). Plausible reaction
mechanism for this transformation involves
a
Horner–
Wadsworth–Emmons (HWE) reaction between ketone 32 and
phosphonate 39 to give enone intermediate 40, its air oxidation
to hemiaminal intermediate 41 upon work-up, and a retro
vinylogous aldol-type bond cleavage to produce lactam 42. The
incapability of hemiaminal 41, the presumed Gu’s biosynthetic
precursor to fluvirosaone A, to furnish the natural product led us
to devise alternative cyclization strategies. The air-sensitivity of
ketone 32 and enone derivative 40 led us to anchor the three-
carbon unit at the C2 position of ketone 32 prior to the
condensative cyclization (Scheme 5). Ketone 32 could be
converted to compound 45 via N-methallylation and subsequent
Stevens [2,3]-rearrangement in the presence of silver triflate and
proton sponge. Ozonolysis of the methylidene moiety of the TFA
salt of 45 afforded diketone 46 in 78% yield. However, attempted
intramolecular aldol condensation of diketone 46 to fluvirosaone
A (13) was not successful under various conditions. Instead, we
Treatment of enamine 50 with N-bromosuccinimide (NBS)
resulted in the formation of bromopentacycles 55 and 56 in 13%
and 41% yield, respectively. The structure of pentacyclic
bromide 56 was confirmed by a single crystal X-ray analysis. In
contrast to the high convex-face selectivity of the acid-mediated
Scheme 5. Attempted formation of the E-ring of fluvirosaone A.
5
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RESEARCH ARTICLE
Scheme 6. Construction of the pentacyclic framework of fluvirosaone alkaloids.
cyclization, brominative cyclization showed different trend on
stereoselecitivity. Iminium ions 53 and 54 are plausible
intermediates that lead to products 55 and 56, respectively.
Unlike the aforementioned acid-mediated cyclization, slower
bromination might be the stereo-determining step in this
transformation and the approximate 3:1 ratio between
diastereomers 56 and 55 reflects the preferential bromination
from the convex face.
fluvirosaone A (57) in 82% yield. Synthetic access to 57 left us
with the dehydrogenation at C3′–C3 to access fluvirosaone A
(13). However, stereoelectronic analysis of 57 revealed that the
pseudo axial proton at C1′ is sterically more accessible than that
at C3′. As a result, deprotonation occurred favorably at C1′ of 57
under various conditions and dehydrogenation at C3′–C3 could
not be achieved.
We next proceeded with the ozonolysis of the methylidene
group in bromopentacycle 55 and obtained β-bromoketone 58.
Delightfully, β-elimination of bromide 58 occurred smoothly upon
its treatment with silica gel in acetonitrile to produce (–)-
fluvirosaone A (13, 40% over two steps), the enantiomer of
naturally occurring (+)-fluvirosaone A (13).16 NMR data of our
synthetic fluvirosaone A (13) matched those of the natural
product. We next applied the same synthetic protocol to
bromomethylidene 56. Interestingly, ozonolysis of methylidene
Synthesis of Fluvirosaones A & B
Synthetic access to pentacycles 52, 55, and 56 with
varying oxidation state at C3 and different stereochemistry at C2
and C3 provided us with strategic flexibility during the endgame
toward fluvirosaones A (13) and B (14). Firstly, conversion of
compound 52 to fluvirosaone A (13) was attempted (Scheme 7).
TFA salt of 52 was subjected to ozonolysis to produce “dihydro”-
Scheme 7. Synthesis of ()-fluvirosaones A and B.
6
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RESEARCH ARTICLE
Scheme 8. Synthesis of naturally occurring (+)-fluvirosoanes A and B.
5
6
and subsequent silica gel mediated β-elimination of
precursors of these natural products. 1,2-amine shift-mediated
skeletal rearrangement completed the synthesis of
bromoketone 59 produced (–)-fluvirosaone B (14) in 57% yield
over two steps. NMR data matched those of the natural (+)-
fluvirosaone B (14).16 This observation indicates that 2-epi-
fluvirosaone A (18) undergoes a spontaneous 1,2-amine shift to
afford fluvirosaone B (14) consistent with our initial hypothesis.
We have experimentally shown that the relative stereochemistry
at C2 of fluvirosaone A (13) and 2-epi-fluvirosaone A (18)
dictates the fate of their 1,2-amine shift. We propose that these
newly discovered reactivities are operative in the biogenesis of
fluvirosaones A (13) and B (14).
After establishing the synthetic protocol to access (–)-
fluvirosaones A (13) and B (14) from allosecurinine (3), we
sought to access the natural enantiomers, (+)-fluvirosaones A
and B (Scheme 8). We first synthesized a racemic mixture of
menisdaurilide (60) following a five-step synthetic protocol
reported by Peixto and coworkers.22 Racemate 60 was then
allowed to react with enantiomerically enriched carboxylic acid
secu’amamine
A and fluvirosaone B. Notably, the facile
rearrangement of 2-epi-fluvirosaone A (18) to fluvirosaone B (14)
is the key observation from this study with immediate biogenetic
ramifications. It is important to note that while our synthetic
design was inspired by a biosynthetic proposal to these natural
products, our synthetic studies conversely provide insights to the
biogenetic pathways of these natural products. The inherent
propensity of compound 32 to undergo spontaneous air
oxidation and the inertness of compounds 41 and 46 toward
intramolecular cyclization are invaluable lessons with potential
biosynthetic implications. Novel reactivities discovered during
this study that resulted in the formation of desired and undesired
products have laid the foundation for further explorations of other
high-oxidation state securinega alkaloids. Those will be the
subjects of our forthcoming reports.
61 for the resolution and diastereomer (–)-62 was isolated in
3
5% yield. Subsequent methanolysis of ester 62 produced (–)-
Acknowledgements
menisdaurilide (60) in 90% yield and 93% ee. (–)-Menisdaurilide
(
60) was then transformed to viroallosecurinine (4) following a
This work was supported by Samsung Science and Technology
Foundation under Project Number SSTF-BA1701-13.
procedure reported by Busqué, de March, and coworkers.2
Viroallosecurinine (4) could then be transformed to (+)-
fluvirosaone A (13) and (+)-fluvirosaone B (14) following our
aforementioned five-step protocol. Notably, absolute values of
the specific rotation of our synthetic (+)-fluvirosaones A (13) and
B (14) were significantly higher than those of natural samples
1
Conflict of interest
The authors declare no conflict of interest.
(
0
+
Synthetic 13: +491.2 (c = 0.15, MeOH), natural 13 (+37.7 (c =
.15, MeOH), synthetic 14: +517.9 (c = 0.2, MeOH), natural 14:
17.9 (c = 0.06, MeOH)). Discrepancies in the absolute values
Keywords: alkaloids • biomimetic synthesis • rearrangement •
cyclization • Polonovski reaction
of specific rotation and molar circular dichroism (see the
supporting information for details) of our synthetic (93% ee) and
natural samples reveal that fluvirosaones A (13) and B (14) were
isolated as a mixture of enantiomers from the natural source.
These observations raise intriguing questions regarding the
stereoselectivity in the biosynthesis of securinega alkaloids.34,35
[1]
[2]
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[
[
[
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Conclusion
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[
6]
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52, 620–624.
In conclusion, we have completed a biosynthetically
inspired/inspiring synthesis of secu’amamine
fluvirosaones A (13), and B (14). The pluripotent enamine 20
was accessed by VO(acac) -mediated regioselective
Polonovski reaction. Formal hydration and oxidative [3+2]
cycloaddition reaction of enamine 20 enabled access to
A
(12),
[7]
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Entry for the Table of Contents
Biosynthetically inspiring chemical synthesis: Vanadium-mediated regioselective Polonovski reaction of (viro)allosecurinine N-
oxides afforded the key pluripotent enamine precursors that were further transformed to secu’amamine A, fluvirosaones A and B via
biomimetic 1,2-amine shift and/or formal [3+2] cycloaddition of the enamine as key steps.
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