Alkaloids of the Amaryllidaceae. VI. The Action of Oxidizing Agents on Lycorine and Caranine<sup>1</sup>

Fales, Henry M.; Warnhoff, E. W.; Wildman, W. C.

doi:10.1021/ja01627a032

Cited by 42 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30,47,59 Compound was isolated from whole plant of Pancratium maritimum L. as previously reported in the literature. 47 1 H NMR (400 MHz, CD 3 OD-CD 3 COOD 3:1 v/v): δ 9.32 (s, H-7), 7.96 (s, H-11), 7.66 (s, H-8), 7.33 (dt, J = 1.8 and 1.8 Hz, H-3) 6.36 (s, H 2 -11), 5.22 (t, J = 7.0 Hz, H 2 -5), 3.73 (td, J = 7.0, 1.8 Hz, H 2 -4).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

et al. 2009

View full text Add to dashboard Cite

Twenty-two lycorine-related compounds were investigated for in vitro anti-tumor activity using four cancer cell lines displaying different levels of resistance to pro-apoptotic stimuli and two cancer cell lines sensitive to pro-apoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro anti-tumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at non-toxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to pro-apoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, metastatic cancers, among others.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Mp 268-270 °C (lit. 59 mp 260-270 decomp. ); UV (0.1 N NaOH) nm (log ε): 405 (3.90), 272 (4.57); IR (nujol) 1615 cm -1 ; EI MS, m/z : 265 [M] + , 264.…”

Section: Methodsmentioning

confidence: 99%

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

et al. 2009

View full text Add to dashboard Cite

show abstract

“…To access homo-allylic alcohol 2, carbocyclic amide 7 was initially hydrolysed with sodium hydroxide. The resulting amine was then coupled with 6-bromopiperonylic acid 18 using EDCI and this gave the corresponding amide 15 in 79% yield over the two steps. Mori and co-workers during their synthesis of (+)-γ-lycorane showed that an intramolecular Heck reaction Scheme 1 Proposed route to novel 7-deoxypancratistatin analogues.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective synthesis of functionalised carbocyclic amides: construction of the syn-(4aS,10bS)-phenanthridone skeleton

et al. 2012

View full text Add to dashboard Cite

A new synthetic approach has been developed for the preparation of 7-deoxypancratistatin analogues bearing a syn-(4aS,10bS)-phenanthridone ring junction. A one-pot tandem process involving a substrate-directed Overman rearrangement and ring closing metathesis reaction was developed for the stereoselective synthesis of a carbocyclic allylic trichloroacetamide. Conversion to a 6-bromopiperonyl amide, followed by a Heck reaction generated a homoallylic alcohol and completed the syn-(4aS,10bS)-phenanthridone carbon skeleton. Stereoselective epoxidation and dihydroxylation of the syn-(4aS,10bS)-phenanthridone framework was then investigated leading to the preparation of new analogues of 7-deoxypancratistatin.

show abstract

“…Lycorine alkaloids have demonstrated antitumor and antiviral activities (De Leo et al, 1973 ; Chattopadhyay et al, 1984 ; Ghosal et al, 1985 ; Martin, 1987 ). They all contain a tetracyclic pyrrolo[d,e]phenanthridine core and most (including (−)-lycorine) (Fales et al, 1955 ; Takagi et al, 1955 ; Yamada et al, 2009 ) present a trans B/C-ring junction; however, (+)-fortucine (Gorbunova et al, 1984 ; Tokhtabaeva et al, 1987 ), (+)-kirkine (Bastida et al, 1995 ), and (−)-siculinine (Richomme et al, 1989 ) contain a cis ring junction (Figure 11 ).…”

Section: Syntheses Ok Alkaloids Bearing a Cyclic Trisubstituted Alkenmentioning

confidence: 99%

Total synthesis of natural products using hypervalent iodine reagents

2015

View full text Add to dashboard Cite

We present a review of natural product syntheses accomplished in our laboratory during the last 5 years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the “aromatic ring umpolung” concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol), a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor), acetylaspidoalbidine (an antitumor agent), fortucine (antiviral and antitumor), erysotramidine (curare-like effect), platensimycin (an antibiotic), and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis). These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

show abstract

Alkaloids of the Amaryllidaceae. VI. The Action of Oxidizing Agents on Lycorine and Caranine¹

Cited by 42 publications

References 0 publications

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

Stereoselective synthesis of functionalised carbocyclic amides: construction of the syn-(4aS,10bS)-phenanthridone skeleton

Total synthesis of natural products using hypervalent iodine reagents

Contact Info

Product

Resources

About

Alkaloids of the Amaryllidaceae. VI. The Action of Oxidizing Agents on Lycorine and Caranine1

Cited by 42 publications

References 0 publications

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Antitumor Activity in Cancer Cells That Display Resistance to Proapoptotic Stimuli: An Investigation of Structure−Activity Relationship and Mechanistic Insight

Stereoselective synthesis of functionalised carbocyclic amides: construction of the syn-(4aS,10bS)-phenanthridone skeleton

Total synthesis of natural products using hypervalent iodine reagents

Contact Info

Product

Resources

About

Alkaloids of the Amaryllidaceae. VI. The Action of Oxidizing Agents on Lycorine and Caranine¹