Homoisoflavonoid

Homoisoflavonoids (3-benzylidenechroman-4-ones) are a type of phenolic compounds occurring naturally^[1] in plants.

Chemical structure of the 3,4-dihydroxyhomoisoflavan sappanol.

Chemically, they have the general structure of a 16-carbon skeleton, which consists of two phenyl rings (A and B) and heterocyclic ring (C).

Synthesis

Homoisoflavones can be synthesized from 2'-hydroxydihydrochalcones.^[2]

Homoisoflavanones can be synthesized^[3] from 3,5-methoxy phenols via chroman-4-one in three steps^[4] or from phloroglucinol.^[5]

Conversion

Homoisoflavanes can be obtained from the conversion of homoisoflavonoids.^[6]

Natural occurrences

The homoisoflavonoids portulacanones A, B, C and D can be found in Portulaca oleracea (common purslane, Caryophyllales, Portulacaceae).^[7]

The 3,4-dihydroxyhomoisoflavans sappanol, episappanol, 3'-deoxysappanol, 3'-O-methylsappanol and 3'-O-methylepisappanol can be found in Caesalpinia sappan.^[8]

The homoisoflavones scillavones A and B can be isolated from the bulbs of Scilla scilloides (Barnardia japonica).^[9]

Homoisoflavanones

 

Chemical structure of sappanone A.

Homoisoflavanones (3-Benzyl-4-chromanones^[10]) can be found in various plants,^[11] notably in Hyacinthaceae (Scilloideae).^[12]

Sappanone A can be found in Caesalpinia sappan.^[13]

C-Methylated homoisoflavanones (3-(4'-methoxy-benzyl)-5,7-dihydroxy-6-methyl-8-methoxy-chroman-4-one, 3-(4'-methoxy-benzyl)-5,7-dihydroxy-6,8-dimethyl-chroman-4-one, 3-(4'-hydroxy-benzyl)-5,7-dihydroxy-6,8-dimethyl-chroman-4-one, 3-(4'-hydroxy-benzyl)-5,7-dihydroxy-6-methyl-8-methoxy-chroman-4-one and 3-(4'-hydroxy-benzyl)-5,7-dihydroxy-6-methyl-chroman-4-one) can be found in the rhizomes of Polygonum odoratum.^[14]

5,7-Dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-chroman-4-one, a homoisoflavanone extracted from Cremastra appendiculata (Orchidaceae), has anti-angiogenic activities and inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-?B nuclear localization.^[15]

In Asparagaceae

3-(4'-Methoxybenzyl)-7,8-methylenedioxy-chroman-4-one, a homoisoflavanone with antimycobacterial activity, can be isolated from Chlorophytum inornatum (Asparagaceae, Agavoideae).^[6]

5,7-Dihydroxy-3-(4-methoxybenzyl)-chroman-4-one, 7-hydroxy-3-(4-hydroxybenzyl)-chroman-4-one and 4’-demethyl-3,9-dihydro-punctatin can be isolated from Agave tequilana (Asparagaceae, Agavoideae).^[16]

in Scilloideae (Hyacinthaceae)

7-O-α-Rhamnopyranosyl-(1→6)-β-glucopiranosyl-5-hydroxy-3-(4-methoxybenzyl)-chroman-4-one, 7-O-α-rhamnopyranosyl-(1→6)-β-glucopiranosyl-5-hydroxy-3-(4′-hydroxybenzyl)-chroman-4-one, 5,7-dihydroxy-3-(4′-methoxybenzyl)-chroman-4-one (3,9-dihidroeucomin), 5,7-dihydroxy-6-methoxy-3-(4′-methoxybenzyl)-chroman-4-one, 5,7-dihydroxy 3-(4′-hydroxybenzyl)-chroman-4-one (4,4′-demethyl-3,9-dihydropuctatin), 5,7-dihydroxy-3-(4′-hydroxybenzyl)-6-methoxy-chroman-4-one (3,9-dihydroeucomnalin) and 7-hydroxy-3-(4′-hydroxybenzyl)-5-methoxy-chroman-4-one can be isolated from the bulbs of Ledebouria floribunda (tribe Hyacintheae).^[17] Other compounds can be found in Ledebouria revoluta, a plant widely used as an ethnomedicinal in southern Africa.^[10]

The homoisoflavanone glycosides (-)-7-O-methyleucomol 5-O-beta-D-glucopyranoside, (-)-7-O-methyleucomol 5-O-beta-rutinoside and (-)-7-O-methyleucomol 5-O-beta-neohesperidoside can be isolated from the bulbs of Ornithogalum caudatum (tribe Ornithogaloideae).^[18]

Scillascillin-type homoisoflavanones (3-hydroxy-type homoisoflavonoids) can be isolated from Drimiopsis maculata (tribe Hyacintheae, Massoniinae).^[19]

Eucomin, eucomol,^[20] (E)-7-O-methyl-eucomin, (—)-7-O-methyleucomol, (+)-3,9-dihydro-eucomin and 7-O-methyl-3,9-dihydro-eucomin^[21] can be isolated from the bulbs of Eucomis bicolor (tribe Hyacintheae, Massoniinae). 4′-o-Methyl-punctatin, autumnalin and 3,9-dihydro-autumnalin can be found in Eucomis autumnalis.^[22]

Five homoisoflavanones, 3,5-dihydroxy-7,8-dimethoxy-3-(3',4'-dimethoxybenzyl)-4-chromanone, 3,5-dihydroxy-7-methoxy-3-(3',4'-dimethoxybenzyl)-4-chromanone, 3,5-dihydroxy-7,8-dimethoxy-3-(3'-hydroxy-4'-methoxybenzyl)-4-chromanone, 3,5,6-trihydroxy-7-methoxy-3-(3'-hydroxy-4'-methoxybenzyl)-4-chromanone and 3,5,7-trihydroxy-3-(3'-hydroxy-4'methoxybenzyl)-4-chromanone, can be isolated from the dichloromethane extract of the bulbs of Pseudoprospero firmifolium (tribe Hyacintheae, subtribe Pseudoprospero).^[23]

A homoisoflavanone can also be found in Albuca fastigiata (tribe Ornithogaleae).^[24]

The same molecule, 5,6-dimethoxy-7-hydroxy-3-(4′-hydroxybenzyl)-4-chromanone, can be found in the bulbs of Resnova humifusa and Eucomis montana (tribe Hyacintheae, subtribe Massoniinae).^[25]

Uses

The homoisoflavonoids portulacanones A, B, C and D show in vitro cytotoxic activities towards four human cancer cell lines.^[7]

See also

• Flavonoids and isoflavonoids, related chemicals with a 15-carbon skeleton

References

1. Roshanak Namdar and Shohreh Nafisi (December 2013). Study on the interaction of homoisoflavonoids with nucleic acids Comparative study by spectroscopic methods. Lap Lambert Academic Publishing GmbH KG. ISBN 978-3-659-49924-1.
2. Rao, Vallabhaneni Madhava; Damu, Guri Lakshmi Vasantha; Sudhakar, Dega; Siddaiah, Vidavaluri; Rao, Chunduri Venkata (2008). "New efficient synthesis and bioactivity of homoisoflavonoids". Arkivoc. 2008 (11): 285–294. doi:10.3998/ark.5550190.0009.b28. hdl:2027/spo.5550190.0009.b28.
3. Jain, Amolak C.; Anita Mehta (née Sharma), (Mrs) (1985). "A new synthesis of homoisoflavanones (3-benzyl-4-chromanones)". Tetrahedron. 41 (24): 5933–5937. doi:10.1016/S0040-4020(01)91433-4.
4. Shaikh, Mahidansha; Petzold, Katja; Kruger, Hendrik G.; Du Toit, Karen (2010). "Synthesis and NMR elucidation of homoisoflavanone analogues". Structural Chemistry. 22: 161–166. doi:10.1007/s11224-010-9703-x.
5. Rawal, Viresh H.; Cava, Michael P. (1983). "Synthesis of scillascillin, a naturally occurring benzocyclobutene". Tetrahedron Letters. 24 (50): 5581–5584. doi:10.1016/S0040-4039(00)94146-7.
6. Zhang, L; Zhang, W. G.; Kang, J; Bao, K; Dai, Y; Yao, X. S. (2008). "Synthesis of (+/-) homoisoflavanone and corresponding homoisoflavane". Journal of Asian Natural Products Research. 10 (9–10): 909–913. doi:10.1080/10286020802217499. PMID 19003606.
7. Yan, Jian; Sun, Li-Rong; Zhou, Zhong-Yu; Chen, Yu-Chan; Zhang, Wei-Min; Dai, Hao-Fu; Tan, Jian-Wen (2012). "Homoisoflavonoids from the medicinal plant Portulaca oleracea". Phytochemistry. 80: 37–41. doi:10.1016/j.phytochem.2012.05.014. PMID 22683318.
8. Namikoshi, Michio; Nakata, Hiroyuki; Yamada, Hiroyuki; Nagai, Minako; Saitoh, Tamotsu (1987). "Homoisoflavonoids and related compounds. II. Isolation and absolute configurations of 3,4-dihydroxylated homoisoflavans and brazilins from Caesalpinia sappan L". Chemical & Pharmaceutical Bulletin. 35 (7): 2761–2773. doi:10.1248/cpb.35.2761.
9. Nishida, Y; Eto, M; Miyashita, H; Ikeda, T; Yamaguchi, K; Yoshimitsu, H; Nohara, T; Ono, M (2008). "A new homostilbene and two new homoisoflavones from the bulbs of Scilla scilloides". Chemical & Pharmaceutical Bulletin. 56 (7): 1022–5. doi:10.1248/cpb.56.1022. PMID 18591825.
10. Moodley, N.; Crouch, N.R.; Mulholland, D.A; Slade, D.; Ferreira, D. (2006). "3-Benzyl-4-chromanones (homoisoflavanones) from bulbs of the ethnomedicinal geophyte Ledebouria revoluta (Hyacinthaceae)". South African Journal of Botany. 72 (4): 517–520. doi:10.1016/j.sajb.2006.01.004.
11. Du Toit, Karen; Drewes, Siegfried E.; Bodenstein, Johannes (2010). "The chemical structures, plant origins, ethnobotany and biological activities of homoisoflavanones". Natural Product Research. 24 (5): 457–490. doi:10.1080/14786410903335174. PMID 20306368.
12. Du Toit, K.; Elgorashi, E.E.; Malan, S.F.; Mulholland, D.A.; Drewes, S.E.; Van Staden, J. (2007). "Antibacterial activity and QSAR of homoisoflavanones isolated from six Hyacinthaceae species". South African Journal of Botany. 73 (2): 236–241. doi:10.1016/j.sajb.2007.01.002.
13. Chang, T. S.; Chao, S. Y.; Ding, H. Y. (2012). "Melanogenesis Inhibition by Homoisoflavavone Sappanone a from Caesalpinia sappan". International Journal of Molecular Sciences. 13 (8): 10359–10367. doi:10.3390/ijms130810359. PMC 3431864. PMID 22949866.
14. Wang, D; Li, D; Zhu, W; Peng, P (2009). "A new C-methylated homoisoflavanone and triterpenoid from the rhizomes of Polygonatum odoratum". Natural Product Research. 23 (6): 580–9. doi:10.1080/14786410802560633. PMID 19384735.
15. Hur, Seulgi; Lee, Yun Sang; Yoo, Hyun; Yang, Jeong-Hee; Kim, Tae-Yoon (2010). "Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-κB nuclear localization". Journal of Dermatological Science. 59 (3): 163–169. doi:10.1016/j.jdermsci.2010.07.001. PMID 20724116.
16. Morales-Serna, José Antonio; Jiménez, Armando; Estrada-Reyes, Rosa; Marquez, Carmen; Cárdenas, Jorge; Salmón, Manuel (2010). "Homoisoflavanones from Agave tequilana Weber". Molecules. 15 (5): 3295–3301. doi:10.3390/molecules15053295. PMC 6263332. PMID 20657479.
17. Calvo, María Isabel (2009). "Homoisoflavanones from Ledebouria floribunda". Fitoterapia. 80 (2): 96–101. doi:10.1016/j.fitote.2008.10.006. PMID 19027834.
18. Tang, Y; Yu, B; Hu, J; Wu, T; Hui, H (2002). "Three new homoisoflavanone glycosides from the bulbs of Ornithogalum caudatum". Journal of Natural Products. 65 (2): 218–20. doi:10.1021/np010466a. PMID 11858761.
19. Koorbanally, C; Crouch, N. R.; Mulholland, D. A. (2001). "Scillascillin-type homoisoflavanones from Drimiopsis maculata (Hyacinthaceae)". Biochemical Systematics and Ecology. 29 (5): 539–541. doi:10.1016/s0305-1978(00)00073-9. PMID 11274776.
20. Heller, W.; Tamm, Ch. (1981). "Homoisoflavanones and Biogenetically Related Compounds". Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products. Vol. 40. pp. 105–152. doi:10.1007/978-3-7091-8611-4_3. ISBN 978-3-7091-8613-8.
21. Heller, Werner; Andermatt, Paul; Schaad, Werner A.; Tamm, Christoph (1976). "Homoisoflavanone. IV. Neue Inhaltsstoffe der Eucomin-Reihe von Eucomis bicolor". Helvetica Chimica Acta. 59 (6): 2048–2058. doi:10.1002/hlca.19760590618. PMID 1017955.
22. Sidwell, W.T.L.; Tamm, Ch. (1970). "The homo-isoflavones II1). Isolation and structure of 4′-o-methyl-punctatin, autumnalin and 3,9-dihydro-autumnalin". Tetrahedron Letters. 11 (7): 475–478. doi:10.1016/0040-4039(70)89003-7.
23. Koorbanally, C; Sewjee, S; Mulholland, D. A.; Crouch, N. R.; Dold, A (2007). "Homoisoflavanones from Pseudoprospero firmifolium of the monotypic tribe Pseudoprospereae (Hyacinthaceae: Hyacinthoideae)". Phytochemistry. 68 (22–24): 2753–6. doi:10.1016/j.phytochem.2007.08.005. PMID 17884116.
24. Koorbanally, Chantal; Mulholland, Dulcie A.; Crouch, Neil R. (2005). "A novel 3-hydroxy-3-benzyl-4-chromanone-type homoisoflavonoid from Albuca fastigiata (Ornithogaloideae: Hyacinthaceae)". Biochemical Systematics and Ecology. 33 (5): 545–549. doi:10.1016/j.bse.2004.08.009.
25. Koorbanally, Neil A.; Crouch, Neil R.; Harilal, Avinash; Pillay, Bavani; Mulholland, Dulcie A. (2006). "Coincident isolation of a novel homoisoflavonoid from Resnova humifusa and Eucomis montana (Hyacinthoideae: Hyacinthaceae)". Biochemical Systematics and Ecology. 34 (2): 114–118. doi:10.1016/j.bse.2005.08.003.