Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation.

Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC.

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Background: Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC.

Objectives: We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy.

AgSbF-catalyzed C3 -Friedel-Crafts alkylation of ,-acetals with indoles for the synthesis of indole substituted pyrrolidine and piperidine derivatives.

An efficient approach to access chiral indole substituted pyrrolidine and piperidine skeletons has been developed through a AgSbF-catalyzed -Friedel-Crafts alkylation of ,-acetals 6a, 6b, 9, and 11a-11d with indoles. As a result, a series of 2,3- indole substituted pyrrolidines 8a-8x and piperidines 10a-10j were prepared in moderate to excellent yields and with excellent diastereoselectivities ( up to 99 : 1). Moreover, several 2,5- indole substituted pyrrolidine derivatives 12a-12k were synthesized according to this strategy with moderate to good yields and diastereoselectivities ( up to 99 : 1).

SmI-mediated intermolecular addition-elimination of piperidine and pyrrolidine -α-radicals with arylacetylene sulfones.

An efficient approach to access α-arylacetylene-substituted pyrrolidine and piperidine derivatives has been developed through a samarium diiodide-mediated addition-elimination process of pyrrolidine and piperidine -α-radicals with arylacetylene sulfones.

Palladium-Catalyzed Sequential Heck Reactions of Olefin-Tethered Aryl Iodides with Alkenes.

An efficient approach to functionalized ()-3-cinnamyl-3-methyl-2,3-dihydrobenzofurans and ()-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-2-enones has been developed through a Pd-catalyzed one-pot cascade process involving two sequential Heck reactions, that is, an intramolecular Heck reaction of olefin-tethered aryl iodides and an intermolecular Heck reaction with substituted styrenes and α,β-unsaturated ketones. As a result, a series of desired products were obtained in moderate to good yields and with exclusive -form selectivities.

In(OTf)-catalyzed -α phosphonylation of ,-acetals with triethyl phosphite.

A practical approach to α-aminophosphonates has been developed through an In(OTf)-catalyzed -α phosphonylation of ,-acetals with triethyl phosphite 7. Indoline and isoindoline ,-acetals 6a-6j and 9a-9j and chain ,-acetals 11a-11p were subjected to a Lewis acid catalyzed -α phosphonylation process. As a result, the desired α-aminophosphonates 8a-8j, 10a-10j and 12a-12p were obtained in moderate to good yields.

AgNTf catalyzed cycloaddition of -acyliminium ions with alkynes for the synthesis of the 3,4-dihydro-1,3-oxazin-2-one skeleton.

A catalyzed process for the synthesis of the 4,6-substituted 3,4-dihydro-1,3-oxazin-2-one skeleton has been developed through cycloaddition of generated acyliminium intermediates with alkynes. A range of chain ,-acetals and terminal alkynes were amenable for this mild transformation. As a result, a series of desired cycloaddition products were obtained in moderate to good yields.

Cu(OTf)-catalyzed C3 aza-Friedel-Crafts alkylation of indoles with ,-acetals.

An efficient approach to access functionalized indole derivatives has been developed through Cu(OTf)-catalyzed C3 aza-Friedel-Crafts alkylation of substituted indoles 5a-5m, -methyl-pyrrole with linear ,-acetals 4a-4l. As a result, a series of C3 amide aza-alkylated indole derivatives 6a-6ag and 7 were synthesized in moderate to excellent yields.

AgNTf-Catalyzed Regioselective C-H Alkenylation of -Dialkylanilines with Ynamides.

Regioselective C-H alkenylation of -dialkylanilines with ynamides was developed using AgNTf as a catalyst. This approach represents a facile hydroarylation of ynamides, allowing for the introduction of an alkenyl group exclusively at the position of aniline derivatives. As a result, a series of 4-alkenyl -dialkylanilines were synthesized with excellent regioselectivities.

TMSOTf-mediated synthesis of skipped dienes through the addition of olefins to imines and semicyclic ,-acetals.

A novel approach to skipped dienes has been developed through the TMSOTf-mediated one-pot addition-substitution of olefins 2a, 2f and 2g with imines 1a-1g, and a series of aryl substituted skipped dienes 3aa-3gf were accordingly obtained in 62%-94% yields. Moreover, semicyclic ,-acetals 5 and 7 could also undergo this transformation to produce the corresponding skipped dienes 6aa and 6af-6al and 8ba and 8bf-8bk in moderate to good yields.

Cu(OTf) catalyzed Ugi-type reaction of ,-acetals with isocyanides for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides.

The Cu(OTf) catalyzed Ugi-type reactions of ,-acetals with isocyanides have been described for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides. 4-Hydroxy-5-substituted-prolinamides can be obtained in high diastereoselectivities (2,4-/ > 19 : 1) and a stereoselective model was proposed for 2,4- selectivity. Moreover, 4-F-VH 032, a novel analog of the VHL ligand, was conveniently obtained by utilizing the present method.

High SHP2 expression determines the efficacy of PD-1/PD-L1 inhibitors in advanced KRAS mutant non-small cell lung cancer.

Background: Src homology region 2 domain-containing phosphatase 2 (SHP2) is a novel target for Kirsten rat sarcoma oncogene (KRAS) mutant cancer. We retrospectively studied the significance of SHP2 in KRAS mutant non-small cell lung cancer (NSCLC) treated with immunotherapy and its relationship with tumor microenvironment (TME).

Methods: Sixty-one advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled.

A One-Pot Approach to 2-Substituted-2-(Dimethoxyphosphoryl)-Pyrrolidines from Substituted -Butyl 4-Oxobutylcarbamates and Trimethyl Phosphite.

A novel approach to 2-substituted-2-(dimethoxyphosphoryl)-pyrrolidines - and - has been developed, which features a TMSOTf-mediated one-pot intramolecular cyclization and phosphonylation of substituted -butyl 4-oxobutylcarbamates. The major advantages of this method include simple operation under mild reaction conditions, the use of cheap Lewis acid, and good to excellent yields with high diastereoselectivities ( up to 99:1).

Zn(OTf)-catalyzed hydroamination of ynamides with aromatic amines.

The Zn(OTf)-catalyzed hydroamination of ynamides 2a-2l with aromatic amines 1a-1r was developed. This protocol features broad substrate scope of aromatic amines, good functional group tolerance for ynamides, and excellent regioselectivities. As a result, a variety of substituted amidine compounds 3aa-3oa, 3ab-3al and 3pa-3rk were prepared in moderate to excellent yields and with high regioselectivities.

Nickel-Catalyzed Regioselective Hydroamination of Ynamides with Secondary Amines.

The first Ni(OTf)-catalyzed hydroamination of ynamides was developed by reacting with secondary amines ( and ). This protocol features excellent regioselectivity, a broad substrate scope of secondary aryl amines, and good functional group tolerance for ynamides. Using this method, a variety of substituted ethene-1,1-diamine compounds were prepared in moderate to excellent yields with high regioselectivities.

Synthesis of Functionalized Bicyclo[2.2.2]octan-2-ones Skeleton via Tandem Process of Amino Acid Involved Formal [4 + 2] and Decarboxylative-Mannich Sequence.

An efficient approach to a functionalized bicyclo[2.2.2]octan-2-one scaffold has been developed through a one-pot cascade process including amino acid involved successive Michael addition and decarboxylative-Mannich sequence.

Sc(OTf)-catalyzed [3 + 2]-cycloaddition of nitrones with ynones.

An efficient approach to access functionalized (2,3-dihydroisoxazol-4-yl) ketones has been developed by reacting nitrones 4 with ynones 7 or terminal ynones 10 in a one-pot fashion. The reaction went through a formal Sc(OTf)3-catalyzed [3 + 2]-cycloaddition process to generate a number of functionalized (2,3-dihydroisoxazol-4-yl) ketones 11aa-11aw, 11ba-11la and 12aa-12ae in moderate to good yields.

Synthesis of a 3,4-Dihydro-1,3-oxazin-2-ones Skeleton via an Intermolecular [4 + 2] Process of -Acyliminium Ions with Ynamides/Terminal Alkynes.

An approach to access functionalized 3,4-dihydro-1,3-oxazin-2-ones has been developed by reacting semicyclic ,-acetals and with ynamides or terminal alkynes in a one-pot fashion. The reaction went through a formal [4 + 2] cycloaddition process to generate a number of functionalized 3,4-dihydro-1,3-oxazin-2-ones and in yields of 34-97%. In addition, the utility of this transformation was demonstrated by the synthesis of (±)-sedamine .

Synthesis of 1-benzylisoindoline and 1-benzyl-tetrahydroisoquinoline through nucleophilic addition of organozinc reagents to ,-acetals.

A new approach to access 1-benzylisoindoline and 1-benzyl-tetrahydroisoquinoline has been developed through nucleophilic addition of organozinc reagents to N,O-acetals. A number of substituted organozinc reagents were amenable for this transformation, and the desired products were obtained with excellent yields. Moreover, Sc(OTf)3 proved to be an effective catalyst for the formation of 1-benzylisoindoline and 1-benzyl-tetrahydroisoquinoline using such nucleophilic addition.

Gold-Catalyzed Addition--Boc Cleavage-Cyclization of ,-Acetal with Ynamides for Construction of 6-(-Butyldimethylsilyl)oxy-tetrahydropyrrolo[1,2-][1,3]oxazin-1-ones.

A highly efficient gold-catalyzed approach between ,-acetals and ynamides for the construction of 6-(-butyldimethylsilyl)oxy-tetrahydropyrrolo[1,2-][1,3]oxazin-1-ones was developed. This reaction tolerated a wide range of substituted ,acetals and TsN-substituted ynamides, leading to novel heterocycles in moderate to good yields and with excellent diastereoselectivities (dr > 99:1).

Establishment and application of a method of next generation sequencing of 285 genes in lung cancer based on Ion-Proton platform.

Background: The development of "precision medicine" needs a novel genetic screening and diagnostic technique for clinical detection. This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through testing 285 genes by customized next generation sequencing (NGS) on Ion-Proton platform.

Methods: We reviewed the related literature and collected data of genomic alteration that occurred in lung cancer.

Synthesis of Amide Enol Carbamates and Carbonates through Cu(OTf)-Catalyzed Reactions of Ynamides with -Butyl Carbamates/Carbonates.

A highly regioselective approach to access amide enol carbamates and carbonates -, -, and was developed through Cu(OTf)-catalyzed reactions of ynamides with -butyl carbamates and and -butyl carbonates . Moreover, this strategy was successfully applied to generate amide enol carbamates - and - from imides and with ynamides through an -Boc cleavage-addition ring-opening process. A range of substituents was amenable to this transformation, and the desired amide enol carbamates and carbonates were obtained in moderate to good yields.

Low frequency of mutation of epidermal growth factor receptor (EGFR) and arrangement of anaplastic lymphoma kinase (ALK) in primary pulmonary lymphoepithelioma-like carcinoma.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of lung cancer. However, the prevalence of driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, and the response of tyrosine kinase inhibitor (TKIs) in PLELC has not been thoroughly investigated.

Method: We retrospectively reviewed the genetic profiles and treatment course of 330 PLELC patients at the Guangdong Lung Cancer Institute (GLCI) from 1st January, 2008 to 30th December, 2018.