Two Novel Lycopodium Alkaloids from Huperzia serrata

Tan, Chen; Ma, Xiaoqiang; Chen, Guofu; Zhu, Dunming

doi:10.1002/1522-2675(200204)85:4<1058::aid-hlca1058>3.0.co;2-q

Cited by 41 publications

(28 citation statements)

References 2 publications

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“…Finally, 36 was converted into (−)‐huperzine Q ( 1 ) quantitatively by using SmI 2 in the presence of H 2 O, presumably owing to the initial formation of the axial radical followed by protonation to afford the equatorial alcohol . The spectroscopic data of synthetic (−)‐huperzine Q fully matched the reported data …”

Section: Resultssupporting

confidence: 71%

“…Among these compounds, (−)‐huperzine Q ( 1 ), (+)‐lycopladine B ( 2 ), (+)‐lycopladine C ( 3 ), and (−)‐lycopladine D ( 4 ) are four structurally related fawcettimine‐type alkaloids (Figure ). Huperzine Q ( 1 ) was isolated from Huperzia serrata by Zhu and co‐workers in 2002, and it possesses an unprecedented pentacyclic ring system and an aminal moiety . The Takayama group and the Zhao group reported the total syntheses of 1 in 2011 and 2015, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Divergent Total Syntheses of (−)‐Huperzine Q, (+)‐Lycopladine B, (+)‐Lycopladine C, and (−)‐4‐epi‐Lycopladine D

Hong

et al. 2017

Chemistry An Asian Journal

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We report herein our synthetic efforts towards the divergent syntheses of (À)-huperzine Q( 1), (+ +)-lycopladine B (2), (+ +)-lycopladine C( 3), and (À)-lycopladine D( 4). The 10-step total synthesis of (À)-huperzine Q( 1)a nd the first total syntheses of (+ +)-lycopladines B( 2)a nd C( 3)w ere accomplished through as eries of cascade reactions. Our approach involved aM ichael addition/aldol/intramolecular C-alkylation sequence to forge the 6/9 spirocycle ring, and this was followed by an ethylene-accelerated carbonyl-olefin metathesis to construct the common 6/5/9 ring system.F inally,l atestage enamine bromofunctionalization enabled us to access (À)-huperzine Q( 1), (+ +)-lycopladine B( 2), and (+ +)-lycopladine C( 3), and at andem C4-epimerization/retro-Claisenc ondensation furnished (À)-4-epi-lycopladine D( 63). IntroductionThe Lycopodium alkaloids are al arge family of complex natural products.N early 300 compounds have been isolated so far. [1] Owing to their intricate polycyclic skeletons andd iverse bioactivities, the total syntheses of these alkaloids have attracted broad attention from the synthetic community in recent years. [2] Among these compounds, (À)-huperzine Q( 1), (+ +)-lycopladine B( 2), (+ +)-lycopladine C( 3), and (À)-lycopladine D( 4) are four structurally relatedf awcettimine-type alkaloids (Figure 1). HuperzineQ (1)w as isolatedf rom Huperzia serrata by Zhu and co-workersi n2 002, and it possessesa nu nprecedented pentacyclic ring system and an aminal moiety. [3] The Takayama group [4] and the Zhao group [5] reported the total syntheseso f1 in 2011a nd 2015, respectively.( + +)-Lycopladine B (2), (+ +)-lycopladine C( 3), and (À)-lycopladine D( 4)w ere isolated from Lycopodium complanatum by Kobayashi and co-workers in 2006. [6] Whereasb oth (+ +)-lycopladines B( 2)a nd C( 3) contain au nique tetracyclic skeleton with ad ienamine moiety, (À)-lycopladine D( 4)c onsists of ap entacyclic core structure with ac arbinolamine lactone core. In 2013, Zhao and co-workers achievedt he first total synthesis of (À)-lycopladine D( 4). [7] Herein, we describe af ull account of our divergents yntheses of (À)-huperzine Q( 1), (+ +)-lycopladine B( 2), and (+ +)-lycopladine C( 3) [8] as wella so ur synthetic efforts towards (À)-lycopladine D( 4). Retrosynthetic analysisOur retrosynthetic analysisf or (À)-huperzine Q( 1), (+ +)-lycopladine B( 2), (+ +)-lycopladine C( 3), and (À)-lycopladine D( 4)i s outlined in Scheme 1. We envisioned that the aminal moietyi n 1 and the dienamine moieties in 2 and 3 could be derived from enamine intermediates 5 and 6,r espectively.W hereas both 5 and 6 could arise from 7 by aC 4-epimerization/cyclization sequence, diketone 7 could also potentially serve as ac ommon synthetic intermediate for the synthesis of (À)-lycopladine D( 4)t hrough aldehyde 10.T he cyclopentanone ring in 7 could be constructedf rom spirocyclic diketone 8,w hich could be readily accessed from enone 9 through our previously developed Michael addition/aldol/C-alkylation method.Initial synthe...

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Section: Resultssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Divergent Total Syntheses of (−)‐Huperzine Q, (+)‐Lycopladine B, (+)‐Lycopladine C, and (−)‐4‐epi‐Lycopladine D

Hong

et al. 2017

Chemistry An Asian Journal

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“…11) Recent extensive studies on the chemical constituents in Lycopodium plants have resulted in the isolation of a number of new alkaloids having novel and diverse structures. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Recently, we have also isolated several new alkaloids having fawcettimine-related structures from Lycopodium serratum THUNB. [27][28][29] In our continuing investigation of the structurally unique Lycopodium alkaloids from this plant, we have purified and identified ten new alkaloids possessing lycopodine-related skeletons.…”

mentioning

confidence: 99%

Ten New Lycopodium Alkaloids Having the Lycopodane Skeleton Isolated from Lycopodium serratum THUNB.

et al. 2003

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(10), having lycopodine-related structures, were isolated from the club moss Lycopodium serratum THUNB. and their structures were elucidated on the basis of spectroscopic analysis and/or chemical transformation.Key words alkaloid; Lycopodium; structure elucidation; X-ray crystal structure; NMR; chemical transformation Lycoposerramine-G (2) was obtained as a colorless amorphous powder. HR-FAB-MS analysis gave m/z 280.1893 (MϩH) ϩ (D Ϫ2.0 mmu) and established the molecular formula as C 16 H 25 NO 3 , which was one oxygen atom less than 1 described above. The 1 H-and 13 C-NMR (Table 1) spectra of 2, which resembled those of 1 except for the chemical shifts of the carbons adjacent to nitrogen, indicated that 1 was an N-oxide derivative of 2. Actually, when 2 was treated with one equivalent of m-CPBA, lycoposerramine-F (1) was obtained in 63% yield, thereby establishing the structure of the new alkaloid as formula 2.Lycoposerramine-H (3) was obtained as colorless prisms (mp 227-228°C, sublimation). HR-FAB-MS analysis gave m/z 262.1809 (MϩH) ϩ (D ϩ0.2 mmu) and established the molecular formula as C 16 H 23 NO 2 , which indicated that 3 had one extra unsaturated number compared to common lycopodine-type alkaloids.1 H-and 13 C-NMR spectra (see Table 1) as well as DEPT spectra suggested the presence of one ketone, a trisubstituted olefin bearing a methyl group, one sp 3 quaternary carbon, four sp 3 methines (one of which had a hydroxyl function), and seven sp 3 methylenes. 1 H-1 H COSY and HMQC spectra revealed connectivities as shown by the bold line in Fig. 3. Further, allyl couplings between the olefinic proton (d 5.35, H-8) and methyl protons (d 1.58, H-16) and methylene protons (d 1.98, 2.70, H-14), as well as homoallyl coupling between the methyl protons (H-16) and the methine proton (d 2.52, H-7), indicated the presence of a double bond at the C-8 (d 121.6)-C-15 (d 135.9) position of the lycopodine skeleton. The location of the secondary hydroxyl group was inferred from the HMBC cross-peaks between the proton at d 3.78 (d, Jϭ2.7 Hz) and the carbonyl carbon (d 212.4, C-5) and the methine carbon at d 38.7 (C-4). The structure including the stereochemistry of the secondary hydroxyl group at C-6 was determined by X-ray analysis as formula 3 (Fig. 3). This is the first example of a lycopodine-type alkaloid that has a double bond at the C-8-C-15 position.Lycoposerramine-I (4) showed a molecular ion peak at m/z 261 and the molecular formula, C 16 H 23 NO 2 , which was established by HR-FAB-MS [m/z 262.1802 (MϩH) ϩ , D Ϫ0.5 mmu], was identical with that of 3 described above. Comparison of its1 H-and 13 C-NMR spectra (see Table 1) with those of 3 suggested that the two alkaloids were isomers at the position of the secondary hydroxyl group. The chemical shifts at C-10 (d 35.5), C-11 (d 69.2), and C-12 (d 44.6) in 4 as well as the HMBC cross-peak (Fig. 4) between the low-field proton (d 4.34) and the quaternary carbon at C-13 (d 59.7) indicated that the hydroxyl group existed at the C-11 position. The stereochemistry...

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“…Huperzia serrata (Tan et al, 2002a), Huperzia selago (Staerk et al, 2004), Lycopodium serratum (Takayama et al, 2003), Lycopodium serratum var. serratum f. serratum (Inubushi et al, 1967a(Inubushi et al, , 1968a, Lycopodium serratum var.…”

Section: Miyoshianine B (=Lycoposerramine J)mentioning

confidence: 94%